Skip to content
2000
image of A Comprehensive Review of Genetic Risk Factors for Alzheimer’s Disease Development

Abstract

Alzheimer’s Disease (AD) is a progressive neurodegenerative disorder with a complex genetic basis involving both rare mutations and common variants. This review provides a comprehensive synthesis of established and emerging genetic risk factors implicated in AD pathogenesis. Mendelian forms are strongly associated with mutations in APP, PSEN1, and PSEN2, whereas the APOE ε4 allele remains the most robust genetic risk factor for late-onset AD. Recent Genome-Wide Association Studies (GWAS) have uncovered additional susceptibility loci, including TREM2, CLU, ABCA7, and SORL1, which reflect diverse biological pathways such as amyloid metabolism, lipid regulation, and immune response. The review also highlights the roles of epigenetic mechanisms such as DNA methylation and histone modifications, as well as gene-environment interactions in modulating disease risk and progression. Although substantial progress has been made in identifying genetic contributors, translating these findings into clinical applications remains challenging. This article underscores the need for integrative, multi-omic approaches and population-diverse studies to enhance risk prediction and enable personalized interventions for prevention and therapy in AD.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cgt/10.2174/0115665232397101250916050247
2025-09-19
2025-12-14

  • From This Site

    /content/journals/cgt/10.2174/0115665232397101250916050247
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Falsetti L. Molecular research on Alzheimer’s disease. Biomedicines 2023 11 7 1883 10.3390/biomedicines11071883 37509522
    [Google Scholar]
  2. Javaid SF Giebel C Khan MAB Hashim MJ Epidemiology of Alzheimer’s disease and other dementias: Rising global burden and forecasted trends. F1000 Res. 2021 10 425 10.12688/f1000research.50786.1
    [Google Scholar]
  3. Jin J. Research progress and future development directions of Alzheimers disease. Theoretical and Natural Science 2025 77 1 141 148 10.54254/2753‑8818/2024.LA19856
    [Google Scholar]
  4. Zhuang Y. Advances in the principles and treatment of Alzheimer’s disease. Theoretical and Natural Science 2025 75 1 90 95 10.54254/2753‑8818/2024.LA19356
    [Google Scholar]
  5. Woźniak K. Gardian-Baj M. Jung M. et al Alzheimer’s Disease - A Comprehensive Review. J. Educ. Health Sport 2024 56 195 209 10.12775/JEHS.2024.56.013
    [Google Scholar]
  6. Zvěřová M. Clinical aspects of Alzheimer’s disease. Clin. Biochem. 2019 72 3 6 10.1016/j.clinbiochem.2019.04.015 31034802
    [Google Scholar]
  7. Knopman D.S. Amieva H. Petersen R.C. et al Alzheimer disease. Nat. Rev. Dis. Primers 2021 7 1 33 10.1038/s41572‑021‑00269‑y 33986301
    [Google Scholar]
  8. Jia J. Xu J. Liu J. et al Comprehensive management of daily living activities, behavioral and psychological symptoms, and cognitive function in patients with Alzheimer’s disease: A chinese consensus on the comprehensive management of alzheimer’s disease. Neurosci. Bull. 2021 37 7 1025 1038 10.1007/s12264‑021‑00701‑z 34050523
    [Google Scholar]
  9. Golby A. Silverberg G. Race E. et al Memory encoding in Alzheimer’s disease: An fMRI study of explicit and implicit memory. Brain 2005 128 4 773 787 10.1093/brain/awh400 15705615
    [Google Scholar]
  10. Bäckman L. Jones S. Berger A.K. Laukka E.J. Small B.J. Cognitive impairment in preclinical Alzheimer’s disease: A meta-analysis. Neuropsychology 2005 19 4 520 531 10.1037/0894‑4105.19.4.520 16060827
    [Google Scholar]
  11. Burgio L. Interventions for the behavioral complications of Alzheimer’s disease: Behavioral approaches. Int. Psychogeriatr. 1996 8 S1 45 52 (Suppl. 1) 10.1017/S1041610296003079 8934265
    [Google Scholar]
  12. Collins J.D. Henley S.M.D. Suárez-González A. A systematic review of the prevalence of depression, anxiety, and apathy in frontotemporal dementia, atypical and young-onset Alzheimer’s disease, and inherited dementia. Int. Psychogeriatr. 2023 35 9 457 476 10.1017/S1041610220001118 32684177
    [Google Scholar]
  13. Macdonald A.J.D. ABC of mental health: Mental health in old age. BMJ 1997 315 7105 413 417 10.1136/bmj.315.7105.413 9277609
    [Google Scholar]
  14. Förstl H. Kurz A. Clinical features of Alzheimer’s disease. Eur. Arch. Psychiatry Clin. Neurosci. 1999 249 6 288 290 10.1007/s004060050101 10653284
    [Google Scholar]
  15. Zanetti O. Zanieri G. Giovanni G.D. et al Effectiveness of procedural memory stimulation in mild Alzheimer’s disease patients: A controlled study. Neuropsychol. Rehabil. 2001 11 3-4 263 272 10.1080/09602010042000088
    [Google Scholar]
  16. Vu M. Mangal R. Stead T. Lopez-Ortiz C. Ganti L. Impact of Alzheimer’s disease on caregivers in the United States. Health Psychol. Res. 2022 10 3 37454 10.52965/001c.37454 35999976
    [Google Scholar]
  17. von Strauss E. Viitanen M. De Ronchi D. Winblad B. Fratiglioni L. Aging and the occurrence of dementia: Findings from a population-based cohort with a large sample of nonagenarians. Arch. Neurol. 1999 56 5 587 592 10.1001/archneur.56.5.587 10328254
    [Google Scholar]
  18. A Armstrong R. Risk factors for Alzheimer’s disease. Folia Neuropathol. 2019 57 2 87 105 10.5114/fn.2019.85929 31556570
    [Google Scholar]
  19. Alan E. Kerry Z. Sevin G. Molecular mechanisms of Alzheimer’s disease: From therapeutic targets to promising drugs. Fundam. Clin. Pharmacol. 2023 37 3 397 427 10.1111/fcp.12861 36576325
    [Google Scholar]
  20. Ratan Y. Rajput A. Maleysm S. et al An insight into cellular and molecular mechanisms underlying the pathogenesis of neurodegeneration in Alzheimer’s disease. Biomedicines 2023 11 5 1398 10.3390/biomedicines11051398 37239068
    [Google Scholar]
  21. Webers A. Heneka M.T. Gleeson P.A. The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer’s disease. Immunol. Cell Biol. 2020 98 1 28 41 10.1111/imcb.12301 31654430
    [Google Scholar]
  22. Holmes C. The role of adaptive and innate immunity in alzheimer’s disease. In: textbook of immunopsychiatry. 1st ed Khandaker G. Harrison N. Bullmore E. Cambridge University Press 2021 213 232 10.1017/9781108539623.012
    [Google Scholar]
  23. Jorfi M. Maaser-Hecker A. Tanzi R.E. The neuroimmune axis of Alzheimer’s disease. Genome Med. 2023 15 1 6 10.1186/s13073‑023‑01155‑w 36703235
    [Google Scholar]
  24. McKhann G. Drachman D. Folstein M. Katzman R. Price D. Stadlan E.M. Clinical diagnosis of Alzheimer’s disease: Report of the NINCDS—ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease. Neurology 2011 77 4 333 3 10.1212/01.wnl.0000400650.92875.cf 21537908
    [Google Scholar]
  25. Bature F. Guinn B. Pang D. Pappas Y. Signs and symptoms preceding the diagnosis of Alzheimer’s disease: A systematic scoping review of literature from 1937 to 2016. BMJ Open 2017 7 8 e015746 10.1136/bmjopen‑2016‑015746 28851777
    [Google Scholar]
  26. Breijyeh Z. Karaman R. Comprehensive review on alzheimer’s disease: Causes and treatment. Molecules 2020 25 24 5789 10.3390/molecules25245789 33302541
    [Google Scholar]
  27. Grossman M. D’Esposito M. Hughes E. et al Language comprehension profiles in Alzheimer’s disease, multi-infarct dementia, and frontotemporal degeneration. Neurology 1996 47 1 183 189 10.1212/WNL.47.1.183 8710075
    [Google Scholar]
  28. Martin E. Velayudhan L. Neuropsychiatric symptoms in mild cognitive impairment: A literature review. Dement. Geriatr. Cogn. Disord. 2020 49 2 146 155 10.1159/000507078 32289790
    [Google Scholar]
  29. Sachdev P.S. The neuropathological underpinnings of neuropsychiatric symptoms in dementia. Am. J. Geriatr. Psychiatry 2024 32 6 765 767 10.1016/j.jagp.2024.01.024 38311519
    [Google Scholar]
  30. Kociolek A.J. Fernandez K.K. Hernandez M. et al Neuropsychiatric symptoms and trajectories of dependence and cognition in a sample of community-dwelling older adults with dementia. Curr. Alzheimer Res. 2023 20 6 409 419 10.2174/1567205020666230908163414 37694796
    [Google Scholar]
  31. Hart D.J. Craig D. Compton S.A. et al A retrospective study of the behavioural and psychological symptoms of mid and late phase Alzheimer’s disease. Int. J. Geriatr. Psychiatry 2003 18 11 1037 1042 10.1002/gps.1013 14618556
    [Google Scholar]
  32. Devanand DP The interrelations between psychosis, behavioral disturbance, and depression in Alzheimer disease. Alzheimer Dis Assoc Disord 1999 13 S3 8 Suppl. 2 10622673
    [Google Scholar]
  33. Teri L. McCurry S.M. Edland S.D. Kukull W.A. Larson E.B. Cognitive decline in Alzheimer’s disease: A longitudinal investigation of risk factors for accelerated decline. J. Gerontol. A Biol. Sci. Med. Sci. 1995 50A 1 M49 M55 10.1093/gerona/50A.1.M49 7814789
    [Google Scholar]
  34. Ferrari C. Lombardi G. Polito C. et al Alzheimer’s Disease progression: Factors influencing cognitive decline. J. Alzheimers Dis. 2017 61 2 785 791 10.3233/JAD‑170665 29226870
    [Google Scholar]
  35. Tarawneh R. Holtzman D.M. The clinical problem of symptomatic Alzheimer disease and mild cognitive impairment. Cold Spring Harb. Perspect. Med. 2012 2 5 a006148 a8 10.1101/cshperspect.a006148 22553492
    [Google Scholar]
  36. Burke AD Goldfarb D Timely diagnosis of Alzheimer disease.. Clin Psychiatry 2022 83 4 LI21019DH1C 10.4088/JCP.LI21019DH1C 35921505
    [Google Scholar]
  37. Holmes C. Genotype and phenotype in Alzheimer’s disease. Br. J. Psychiatry 2002 180 2 131 134 10.1192/bjp.180.2.131 11823322
    [Google Scholar]
  38. Karch C.M. Goate A.M. Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol. Psychiatry 2015 77 1 43 51 10.1016/j.biopsych.2014.05.006 24951455
    [Google Scholar]
  39. Bird T.D. Genetic aspects of Alzheimer disease. Genet. Med. 2008 10 4 231 239 10.1097/GIM.0b013e31816b64dc 18414205
    [Google Scholar]
  40. Gaugler J. James B. Johnson T. Mair A. Weuve J. 2019 Alzheimer’s disease facts and figures. Alzheimers Dement. 2019 15 3 321 387 10.1016/j.jalz.2019.01.010
    [Google Scholar]
  41. 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020 16 3 391 460 10.1002/alz.12068
    [Google Scholar]
  42. Wong W. Economic burden of Alzheimer disease and managed care considerations. Am. J. Manag. Care 2020 26 8 S177 S183 (Suppl.) 32840331
    [Google Scholar]
  43. Huque H. Eramudugolla R. Chidiac B. Could country-level factors explain sex differences in dementia incidence and prevalence? a systematic review and meta-analysis. J. Alzheimers Dis. 2023 91 4 1231 1241 10.3233/JAD‑220724 36565114
    [Google Scholar]
  44. Lopez OL The growing burden of Alzheimer’s disease.2011; 17: S339-45. (Suppl. 13) PMID: 22214391 Am J Manag Care 2011 17 S339 45 (Suppl. 13) 22214391
     [Google Scholar]
  45. Topping M. Kim J. Fletcher J. Geographic variation in Alzheimer’s disease mortality. PLoS One 2021 16 7 e0254174 10.1371/journal.pone.0254174 34197566
    [Google Scholar]
  46. Wimo A. Winblad B. Aguero-Torres H. von Strauss E. The magnitude of dementia occurrence in the world. Alzheimer Dis. Assoc. Disord. 2003 17 2 63 67 10.1097/00002093‑200304000‑00002 12794381
    [Google Scholar]
  47. Wimo A. Seeher K. Cataldi R. et al The worldwide costs of dementia in 2019. Alzheimers Dement. 2023 19 7 2865 2873 10.1002/alz.12901 36617519
    [Google Scholar]
  48. Lastuka A. Bliss E. Breshock M.R. et al Societal costs of dementia: 204 Countries, 2000–2019. J. Alzheimers Dis. 2024 101 1 277 292 10.3233/JAD‑240163 39150827
    [Google Scholar]
  49. Grabher B.J. Effects of Alzheimer disease on patients and their family. J. Nucl. Med. Technol. 2018 46 4 335 340 10.2967/jnmt.118.218057 30139888
    [Google Scholar]
  50. Blay S.L. Peluso É.T.P. Public stigma: The community’s tolerance of Alzheimer disease. Am. J. Geriatr. Psychiatry 2010 18 2 163 171 10.1097/JGP.0b013e3181bea900 20104072
    [Google Scholar]
  51. Schlag K.E. Vangelisti A.L. Reflections on dementia-related stigma and direct support seeking by family caregivers as mediating associations between caregiver stress, burden, and well-being. Health Commun. 2024 39 12 2474 2485 10.1080/10410236.2023.2270248 37876032
    [Google Scholar]
  52. Crous-Bou M. Minguillón C. Gramunt N. Molinuevo J.L. Alzheimer’s disease prevention: From risk factors to early intervention. Alzheimers Res. Ther. 2017 9 1 71 10.1186/s13195‑017‑0297‑z 28899416
    [Google Scholar]
  53. Angelopoulou E. Paudel Y.N. Papageorgiou S.G. Piperi C. APOE genotype and Alzheimer’s disease: The influence of lifestyle and environmental factors. ACS Chem. Neurosci. 2021 12 15 2749 2764 10.1021/acschemneuro.1c00295 34275270
    [Google Scholar]
  54. Hao X. Wang A. Li C. Shao L. Li Y. Yang P. Genetic association of BIN1 and GAB2 in Alzheimer’s disease: A meta‐analysis and systematic review. Geriatr. Gerontol. Int. 2021 21 2 185 191 10.1111/ggi.14109 33331110
    [Google Scholar]
  55. Cruts M. Theuns J. Van Broeckhoven C. Locus‐specific mutation databases for neurodegenerative brain diseases. Hum. Mutat. 2012 33 9 1340 1344 10.1002/humu.22117 22581678
    [Google Scholar]
  56. Fernández M.V. Kim J.H. Budde J.P. et al Analysis of neurodegenerative Mendelian genes in clinically diagnosed Alzheimer Disease. PLoS Genet. 2017 13 11 e1007045 10.1371/journal.pgen.1007045 29091718
    [Google Scholar]
  57. Pimenova A.A. Raj T. Goate A.M. Untangling genetic risk for Alzheimer’s disease. Biol. Psychiatry 2018 83 4 300 310 10.1016/j.biopsych.2017.05.014 28666525
    [Google Scholar]
  58. Belloy M.E. Napolioni V. Greicius M.D. A quarter century of apoe and alzheimer’s disease: Progress to date and the path forward. Neuron 2019 101 5 820 838 10.1016/j.neuron.2019.01.056 30844401
    [Google Scholar]
  59. Bertram L. McQueen M.B. Mullin K. Blacker D. Tanzi R.E. Systematic meta-analyses of Alzheimer disease genetic association studies: The AlzGene database. Nat. Genet. 2007 39 1 17 23 10.1038/ng1934 17192785
    [Google Scholar]
  60. Day S. Roberts S. Launder N.H. et al Age of symptom onset and longitudinal course of sporadic Alzheimer’s disease, frontotemporal dementia, and vascular dementia: A systematic review and meta-analysis. J. Alzheimers Dis. 2022 85 4 1819 1833 10.3233/JAD‑215360 34958038
    [Google Scholar]
  61. Hou Y. Dan X. Babbar M. et al Ageing as a risk factor for neurodegenerative disease. Nat. Rev. Neurol. 2019 15 10 565 581 10.1038/s41582‑019‑0244‑7 31501588
    [Google Scholar]
  62. De Jager P.L. Shulman J.M. Chibnik L.B. et al A genome-wide scan for common variants affecting the rate of age-related cognitive decline. Neurobiol. Aging 2012 33 5 1017.e1 1017.e15 10.1016/j.neurobiolaging.2011.09.033 22054870
    [Google Scholar]
  63. Naj A.C. Schellenberg G.D. Genomic variants, genes, and pathways of Alzheimer’s disease: An overview. Am. J. Med. Genet. B. Neuropsychiatr. Genet. 2017 174 1 5 26 10.1002/ajmg.b.32499 27943641
    [Google Scholar]
  64. Kunkle B.W. Grenier-Boley B. Sims R. et al Genetic meta-analysis of diagnosed Alzheimer’s disease identifies new risk loci and implicates Aβ, tau, immunity and lipid processing. Nat. Genet. 2019 51 3 414 430 10.1038/s41588‑019‑0358‑2 30820047
    [Google Scholar]
  65. Grant W.B. A brief history of the progress in our understanding of genetics and lifestyle, especially diet, in the risk of Alzheimer’s disease. J. Alzheimers Dis. 2024 100 s1 S165 S178 10.3233/JAD‑240658 39121130
    [Google Scholar]
  66. Rosenthal S.L. Kamboh M.I. Late-Onset Alzheimer’s disease genes and the potentially implicated pathways. Curr. Genet. Med. Rep. 2014 2 2 85 101 10.1007/s40142‑014‑0034‑x 24829845
    [Google Scholar]
  67. Jansen I.E. Savage J.E. Watanabe K. et al Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk. Nat. Genet. 2019 51 3 404 413 10.1038/s41588‑018‑0311‑9 30617256
    [Google Scholar]
  68. Yamazaki Y. Zhao N. Caulfield T.R. Liu C.C. Bu G. Apolipoprotein E and Alzheimer disease: Pathobiology and targeting strategies. Nat. Rev. Neurol. 2019 15 9 501 518 10.1038/s41582‑019‑0228‑7 31367008
    [Google Scholar]
  69. Kasuga K. Shimohata T. Nishimura A. et al Identification of independent APP locus duplication in Japanese patients with early-onset Alzheimer disease. J. Neurol. Neurosurg. Psychiatry 2009 80 9 1050 1052 10.1136/jnnp.2008.161703 19684239
    [Google Scholar]
  70. Van Cauwenberghe C. Van Broeckhoven C. Sleegers K. The genetic landscape of Alzheimer disease: Clinical implications and perspectives. Genet. Med. 2016 18 5 421 430 10.1038/gim.2015.117 26312828
    [Google Scholar]
  71. Lanoiselée H.M. Nicolas G. Wallon D. et al APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017 14 3 e1002270 10.1371/journal.pmed.1002270 28350801
    [Google Scholar]
  72. Floudas C.S. Um N. Kamboh M.I. Barmada M.M. Visweswaran S. Identifying genetic interactions associated with late-onset Alzheimer’s disease. BioData Min. 2014 7 1 35 10.1186/s13040‑014‑0035‑z 25649863
    [Google Scholar]
  73. Gao X. Chen Q. Yao H. et al Epigenetics in Alzheimer’s Disease. Front. Aging Neurosci. 2022 14 911635 10.3389/fnagi.2022.911635 35813941
    [Google Scholar]
  74. Lee J.H. Cheng R. Barral S. et al Identification of novel loci for Alzheimer disease and replication of CLU, PICALM, and BIN1 in Caribbean Hispanic individuals. Arch. Neurol. 2011 68 3 320 328 10.1001/archneurol.2010.292 21059989
    [Google Scholar]
  75. Crehan H. Holton P. Wray S. Pocock J. Guerreiro R. Hardy J. Complement receptor 1 (CR1) and Alzheimer’s disease. Immunobiology 2012 217 2 244 250 10.1016/j.imbio.2011.07.017 21840620
    [Google Scholar]
  76. Nehls M. Unified theory of Alzheimer’s disease (UTAD): Implications for prevention and curative therapy. J. Mol. Psychiatry 2016 4 1 3 10.1186/s40303‑016‑0018‑8 27429752
    [Google Scholar]
  77. Gao Y. Ren R.J. Zhong Z.L. et al Mutation profile of APP, PSEN1, and PSEN2 in Chinese familial Alzheimer’s disease. Neurobiol. Aging 2019 77 154 157 10.1016/j.neurobiolaging.2019.01.018 30822634
    [Google Scholar]
  78. Potter R. Patterson B.W. Elbert D.L. et al Increased in vivo amyloid-β42 production, exchange, and loss in presenilin mutation carriers. Sci. Transl. Med. 2013 5 189 189ra77 10.1126/scitranslmed.3005615 23761040
    [Google Scholar]
  79. Battaglia S. Avenanti A. Vécsei L. Neurodegeneration in Cognitive Impairment and Mood Dis-orders for Experimental, Clinical and Translational Neuropsy-chiatry 2024. Medicine and Pharmacology 2024 12 3 574
    [Google Scholar]
  80. Serrano-Pozo A. Frosch M.P. Masliah E. Hyman B.T. Neuropathological alterations in Alzheimer disease. Cold Spring Harb. Perspect. Med. 2011 1 1 a006189 a9 10.1101/cshperspect.a006189 22229116
    [Google Scholar]
  81. Galasko D. An integrated approach to the management of Alzheimer’s disease: Assessing cognition, function and behaviour. Eur. J. Neurol. 1998 5 S4 10.1111/j.1468‑1331.1998.tb00444.x
    [Google Scholar]
  82. Arber C. Lovejoy C. Harris L. et al Familial Alzheimer’s disease mutations in PSEN1 lead to premature human stem cell neurogenesis. Cell Rep. 2021 34 2 108615 10.1016/j.celrep.2020.108615 33440141
    [Google Scholar]
  83. Parihar M.S. Brewer G.J. Amyloid-β as a modulator of synaptic plasticity. J. Alzheimers Dis. 2010 22 3 741 763 10.3233/JAD‑2010‑101020 20847424
    [Google Scholar]
  84. Cruts M Hendriks L Van Broeckhoven C. The presenilin genes: A new gene family involved in Alzheimer disease pathology. Hum Mol Genet 1996 5 Spec No 1449 55 Supply. 1 10.1093/hmg/5.Supplement_1.1449 8875251
    [Google Scholar]
  85. Shepherd C. McCann H. Halliday G.M. Variations in the neuropathology of familial Alzheimer’s disease. Acta Neuropathol. 2009 118 1 37 52 10.1007/s00401‑009‑0521‑4 19306098
    [Google Scholar]
  86. McMurtray A.M. Ringman J. Chao S.Z. Licht E. Saul R.E. Mendez M.F. Family history of dementia in early‐onset versus very late‐onset Alzheimer’s disease. Int. J. Geriatr. Psychiatry 2006 21 6 597 598 10.1002/gps.1540 16783800
    [Google Scholar]
  87. Goldman J.S. Genetic testing and counseling in the diagnosis and management of young-onset dementias. Psychiatr. Clin. North Am. 2015 38 2 295 308 10.1016/j.psc.2015.01.008 25998117
    [Google Scholar]
  88. Bocchetta M. Mega A. Bernardi L. et al Genetic counseling and testing for Alzheimer’s disease and frontotemporal lobar degeneration: An Italian consensus protocol. J. Alzheimers Dis. 2016 51 1 277 291 10.3233/JAD‑150849 26901402
    [Google Scholar]
  89. Finckh U. Müller-Thomsen T. Mann U. et al High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. Am. J. Hum. Genet. 2000 66 1 110 117 10.1086/302702 10631141
    [Google Scholar]
  90. Brouwers N. Sleegers K. Van Broeckhoven C. Molecular genetics of Alzheimer’s disease: An update. Ann. Med. 2008 40 8 562 583 10.1080/07853890802186905 18608129
    [Google Scholar]
  91. Hardy J. Myers A. Genetic variability in expression of proteins and the risk of sporadic neurologic diseases. Neurology 2007 68 9 632 633 10.1212/01.wnl.0000256793.58438.c4 17325268
    [Google Scholar]
  92. Ruffini N. Klingenberg S. Schweiger S. Gerber S. Common factors in neurodegeneration: A meta-study revealing shared patterns on a multi-omics scale. Cells 2020 9 12 2642 10.3390/cells9122642 33302607
    [Google Scholar]
  93. Andrade-Guerrero J. Santiago-Balmaseda A. Jeronimo-Aguilar P. et al Alzheimer’s Disease: An updated overview of its genetics. Int. J. Mol. Sci. 2023 24 4 3754 10.3390/ijms24043754 36835161
    [Google Scholar]
  94. Neuner S.M. Tcw J. Goate A.M. Genetic architecture of Alzheimer’s disease. Neurobiol. Dis. 2020 143 104976 10.1016/j.nbd.2020.104976 32565066
    [Google Scholar]
  95. Dunn A.R. O’Connell K.M.S. Kaczorowski C.C. Gene-by-environment interactions in Alzheimer’s disease and Parkinson’s disease. Neurosci. Biobehav. Rev. 2019 103 73 80 10.1016/j.neubiorev.2019.06.018 31207254
    [Google Scholar]
  96. Bartoletti-Stella A. Tarozzi M. Mengozzi G. et al Dementia-related genetic variants in an Italian population of early-onset Alzheimer’s disease. Front. Aging Neurosci. 2022 14 969817 10.3389/fnagi.2022.969817 36133075
    [Google Scholar]
  97. Krüger J. Moilanen V. Majamaa K. Remes A.M. Molecular genetic analysis of the APP, PSEN1, and PSEN2 genes in Finnish patients with early-onset Alzheimer disease and frontotemporal lobar degeneration. Alzheimer Dis. Assoc. Disord. 2012 26 3 272 276 10.1097/WAD.0b013e318231e6c7 21959359
    [Google Scholar]
  98. Sims R. Hill M. Williams J. The multiplex model of the genetics of Alzheimer’s disease. Nat. Neurosci. 2020 23 3 311 322 10.1038/s41593‑020‑0599‑5 32112059
    [Google Scholar]
  99. Wang Z.X. Wan Q. Xing A. HLA in Alzheimer’s Disease: Genetic association and possible pathogenic roles. Neuromolecular Med. 2020 22 4 464 473 10.1007/s12017‑020‑08612‑4 32894413
    [Google Scholar]
  100. Chasioti D Yan J Nho K. P2‐147: Polygenic composite scores in Alzheimer’s disease: A systematic review. Alzheimers Dement 2019 15 7S_Part_12
    [Google Scholar]
  101. Clark K. Leung Y.Y. Lee W.P. Voight B. Wang L.S. Polygenic risk scores in Alzheimer’s disease genetics: Methodology, applications, inclusion, and diversity. J. Alzheimers Dis. 2022 89 1 1 12 10.3233/JAD‑220025 35848019
    [Google Scholar]
  102. de Rojas I. Moreno-Grau S. Tesi N. et al Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores. Nat. Commun. 2021 12 1 3417 10.1038/s41467‑021‑22491‑8 34099642
    [Google Scholar]
  103. Liu H. Lutz M. Luo S. Association between polygenic risk score and the progression from mild cognitive impairment to alzheimer’s disease. J. Alzheimers Dis. 2021 84 3 1323 1335 10.3233/JAD‑210700 34657885
    [Google Scholar]
  104. Fan Y. Gao Y. Therriault J. Luo J. Ba M. Zhang H. The Effects of CSF Neurogranin and APOE ε4 on Cognition and Neuropathology in Mild Cognitive Impairment and Alzheimer’s Disease. Front. Aging Neurosci. 2021 13 667899 10.3389/fnagi.2021.667899 33986657
    [Google Scholar]
  105. Agnello L. Gambino C.M. Lo Sasso B. et al Neurogranin as a Novel Biomarker in Alzheimer’s Disease. Lab. Med. 2021 52 2 188 196 10.1093/labmed/lmaa062 32926148
    [Google Scholar]
  106. Seto M. Weiner R.L. Dumitrescu L. Hohman T.J. Protective genes and pathways in Alzheimer’s disease: Moving towards precision interventions. Mol. Neurodegener. 2021 16 1 29 10.1186/s13024‑021‑00452‑5 33926499
    [Google Scholar]
  107. Dourlen P. Kilinc D. Malmanche N. Chapuis J. Lambert J.C. The new genetic landscape of Alzheimer’s disease: From amyloid cascade to genetically driven synaptic failure hypothesis? Acta Neuropathol. 2019 138 2 221 236 10.1007/s00401‑019‑02004‑0 30982098
    [Google Scholar]
  108. Hu Y.S. Xin J. Hu Y. Zhang L. Wang J. Analyzing the genes related to Alzheimer’s disease via a network and pathway-based approach. Alzheimers Res. Ther. 2017 9 1 29 10.1186/s13195‑017‑0252‑z 28446202
    [Google Scholar]
  109. Hardy J. Escott-Price V. Genes, pathways and risk prediction in Alzheimer’s disease. Hum. Mol. Genet. 2019 28 R2 ddz163 10.1093/hmg/ddz163 31332445
    [Google Scholar]
  110. Gan L. Cookson M.R. Petrucelli L. La Spada A.R. Converging pathways in neurodegeneration, from genetics to mechanisms. Nat. Neurosci. 2018 21 10 1300 1309 10.1038/s41593‑018‑0237‑7 30258237
    [Google Scholar]
  111. Zhang Y. Wu B. Chen S. et al Whole exome sequencing analyses identified novel genes for Alzheimer’s disease and related dementia. Alzheimers Dement. 2024 20 10 7062 7078 10.1002/alz.14181
    [Google Scholar]
  112. Tol J. Slooter A.J.C. Van Duijn C.M. Genetic factors in early- and late-onset Alzheimer’s disease. In: Mayeux R, Christen Y, Eds. Epidemiology of Alzheimer’s disease: From gene to prevention springer berlin heidelberg. Berlin, Heidelberg 1999 33 39 10.1007/978‑3‑642‑60076‑0_3
    [Google Scholar]
  113. Emrani S. Arain H.A. DeMarshall C. Nuriel T. APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: A systematic review. Alzheimers Res. Ther. 2020 12 1 141 10.1186/s13195‑020‑00712‑4 33148345
    [Google Scholar]
  114. Agnello L. Gambino C.M. Ciaccio A.M. et al Exploring the effect of APOE ε4 on biomarkers of neurodegeneration in Alzheimer’s disease. Clin. Chim. Acta 2024 562 119876 10.1016/j.cca.2024.119876 39025198
    [Google Scholar]
  115. Zheng B. The inner link between apolipoprotein E and the risk of Alzheimer’s disease. MedScien 2024 1 7
    [Google Scholar]
  116. Santos N.G. Suemoto C.K. Ferretti-Rebustini R.E.L. et al Quantification of encephalic transcripts of the APOE allele specific gene of European and African ancestry. Alzheimers Dement. 2023 19 S12 e076340 10.1002/alz.076340
    [Google Scholar]
  117. Yun W.B. Lee Y.M. Kim Y.J. Lee H. P205: The effect of APOE e4 genotype on cognition, brain volume, glucose metabolism and amyloid deposition in AD. Int. Psychogeriatr. 2023 35 S1 266 267 10.1017/S1041610223004349
    [Google Scholar]
  118. Oveisgharan S. Yu L. de Paiva Lopes K. et al Proteins linking APOE ɛ4 with Alzheimer’s disease. Alzheimers Dement. 2024 20 7 4499 4511 10.1002/alz.13867 38856164
    [Google Scholar]
  119. Moura S. Celis K. Muniz M. et al APOE genotype vs Local ancestry: What contributes the most to Alzheimer’s disease risk? Alzheimers Dement. 2023 19 S12 e079093 10.1002/alz.079093
    [Google Scholar]
  120. Corder E.H. Saunders A.M. Strittmatter W.J. et al Apolipoprotein E, survival in Alzheimer’s disease patients, and the competing risks of death and Alzheimer’s disease. Neurology 1995 45 7 1323 1328 10.1212/WNL.45.7.1323 7617191
    [Google Scholar]
  121. Belloy M.E. Andrews S.J. Guen Y.L. Napolioni V. Greicius M.D. APOE and Alzheimer disease risk across age, sex, race, ethnicity, and ancestry: An overview from 68,756 individuals. Alzheimers Dement. 2023 19 S24 e082772 10.1002/alz.082772
    [Google Scholar]
  122. Patel S. Wei J. Shi Z. et al Refining risk for Alzheimer’s disease among heterozygous APOE ɛ4 carriers. J. Alzheimers Dis. 2023 94 2 483 489 10.3233/JAD‑230156 37334598
    [Google Scholar]
  123. Coon K.D. Myers A.J. Craig D.W. et al A high-density whole-genome association study reveals that APOE is the major susceptibility gene for sporadic late-onset Alzheimer’s disease. J. Clin. Psychiatry 2007 68 4 613 618 10.4088/JCP.v68n0419 17474819
    [Google Scholar]
  124. Colonna M. Wang Y. TREM2 variants: New keys to decipher Alzheimer disease pathogenesis. Nat. Rev. Neurosci. 2016 17 4 201 207 10.1038/nrn.2016.7 26911435
    [Google Scholar]
  125. Ulrich J.D. Ulland T.K. Colonna M. Holtzman D.M. Elucidating the role of TREM2 in Alzheimer’s disease. Neuron 2017 94 2 237 248 10.1016/j.neuron.2017.02.042 28426958
    [Google Scholar]
  126. Guerreiro R. Wojtas A. Bras J. et al TREM2 variants in Alzheimer’s disease. N. Engl. J. Med. 2013 368 2 117 127 10.1056/NEJMoa1211851 23150934
    [Google Scholar]
  127. Roses A.D. Apolipoprotein E alleles as risk factors in Alzheimer’s disease. Annu. Rev. Med. 1996 47 1 387 400 10.1146/annurev.med.47.1.387 8712790
    [Google Scholar]
  128. Pantelidis P. Lambert-Hammill M. Wierzbicki A.S. Simple sequence-specific-primer-PCR method to identify the three main apolipoprotein E haplotypes. Clin. Chem. 2003 49 11 1945 1948 10.1373/clinchem.2003.021683 14578332
    [Google Scholar]
  129. Liu C.C. Kanekiyo T. Xu H. Bu G. Bu G. Apolipoprotein E and Alzheimer disease: Risk, mechanisms and therapy. Nat. Rev. Neurol. 2013 9 2 106 118 10.1038/nrneurol.2012.263 23296339
    [Google Scholar]
  130. Raber J. Wong D. Buttini M. et al Isoform-specific effects of human apolipoprotein E on brain function revealed in ApoE knockout mice: Increased susceptibility of females. Proc. Natl. Acad. Sci. USA 1998 95 18 10914 10919 10.1073/pnas.95.18.10914 9724804
    [Google Scholar]
  131. Hashimoto T. Serrano-Pozo A. Hori Y. et al Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid β peptide. J. Neurosci. 2012 32 43 15181 15192 10.1523/JNEUROSCI.1542‑12.2012 23100439
    [Google Scholar]
  132. Ma F.C. Zong Y. Wang H.F. Li J.Q. Cao X.P. Tan L. ABCA7 genotype altered Aβ levels in cerebrospinal fluid in Alzheimer’s disease without dementia. Ann. Transl. Med. 2018 6 22 437 10.21037/atm.2018.07.04 30596067
    [Google Scholar]
  133. Tzioras M. Davies C. Newman A. Jackson R. Spires-Jones T. Invited Review: APOE at the interface of inflammation, neurodegeneration and pathological protein spread in Alzheimer’s disease. Neuropathol. Appl. Neurobiol. 2019 45 4 327 346 10.1111/nan.12529 30394574
    [Google Scholar]
  134. Stocker H. Möllers T. Perna L. Brenner H. The genetic risk of Alzheimer’s disease beyond APOE ε4: Systematic review of Alzheimer’s genetic risk scores. Transl. Psychiatry 2018 8 1 166 10.1038/s41398‑018‑0221‑8 30143603
    [Google Scholar]
  135. Huq A.J. Fransquet P. Laws S.M. et al Genetic resilience to Alzheimer’s disease in APOE ε4 homozygotes: A systematic review. Alzheimers Dement. 2019 15 12 1612 1623 10.1016/j.jalz.2019.05.011 31506248
    [Google Scholar]
  136. Tanaka S. Ueda K. APOE gene e4 allele accelerates the atrophy of the inferior temporal lobe in Alzheimer’s disease (BIOORGANIC CHEMISTRY-Molecular Clinical Chemistry). ICR Annu Rep Institute for Chemical Research. Kyoto University 1998 4 42 43
    [Google Scholar]
  137. Abushakra S. Porsteinsson A.P. Sabbagh M. et al APOE ε4/ε4 homozygotes with early Alzheimer’s disease show accelerated hippocampal atrophy and cortical thinning that correlates with cognitive decline. Alzheimers Dement. (N. Y.) 2020 6 1 e12117 10.1002/trc2.12117 33304988
    [Google Scholar]
  138. Albert M. Soldan A. Gottesman R. et al Cognitive changes preceding clinical symptom onset of mild cognitive impairment and relationship to ApoE genotype. Curr. Alzheimer Res. 2014 11 8 773 784 10.2174/156720501108140910121920 25212916
    [Google Scholar]
  139. Schipper H.M. Apolipoprotein E. Apolipoprotein E. Implications for AD neurobiology, epidemiology and risk assessment. Neurobiol. Aging 2011 32 5 778 790 10.1016/j.neurobiolaging.2009.04.021 19482376
    [Google Scholar]
  140. Freudenberg-Hua Y. Li W. Davies P. The role of genetics in advancing precision medicine for Alzheimer’s disease—A narrative review. Front. Med. (Lausanne) 2018 5 108 10.3389/fmed.2018.00108 29740579
    [Google Scholar]
  141. Berkowitz C.L. Mosconi L. Rahman A. Scheyer O. Hristov H. Isaacson R.S. Clinical application of APOE in Alzheimer’s prevention: A precision medicine approach. J. Prev. Alzheimers Dis. 2018 5 4 245 252 10.14283/jpad.2018.35 30298183
    [Google Scholar]
  142. O’Donoghue M.C. Murphy S.E. Zamboni G. Nobre A.C. Mackay C.E. APOE genotype and cognition in healthy individuals at risk of Alzheimer’s disease: A review. Cortex 2018 104 103 123 10.1016/j.cortex.2018.03.025 29800787
    [Google Scholar]
  143. Rajabli F. Feliciano B.E. Celis K. et al Ancestral origin of ApoE ε4 Alzheimer disease risk in Puerto Rican and African American populations. PLoS Genet. 2018 14 12 e1007791 10.1371/journal.pgen.1007791 30517106
    [Google Scholar]
  144. Miyashita A. Kikuchi M. Hara N. Ikeuchi T. Genetics of Alzheimer’s disease: An East Asian perspective. J. Hum. Genet. 2023 68 3 115 124 10.1038/s10038‑022‑01050‑z 35641666
    [Google Scholar]
  145. Lancaster C. Tabet N. Rusted J. The elusive nature of APOE ε4 in mid-adulthood: Understanding the cognitive profile. J. Int. Neuropsychol. Soc. 2017 23 3 239 253 10.1017/S1355617716000990 28059047
    [Google Scholar]
  146. Abondio P. Sazzini M. Garagnani P. et al The genetic variability of APOE in different human populations and its implications for longevity. Genes (Basel) 2019 10 3 222 10.3390/genes10030222 30884759
    [Google Scholar]
  147. Li R.Y. Qin Q. Yang H.C. et al TREM2 in the pathogenesis of AD: A lipid metabolism regulator and potential metabolic therapeutic target. Mol. Neurodegener. 2022 17 1 40 10.1186/s13024‑022‑00542‑y 35658903
    [Google Scholar]
  148. Kleinberger G. Yamanishi Y. Suárez-Calvet M. et al TREM2 mutations implicated in neurodegeneration impair cell surface transport and phagocytosis. Sci. Transl. Med. 2014 6 243 243ra86 10.1126/scitranslmed.3009093 24990881
    [Google Scholar]
  149. Hsieh C.L. Koike M. Spusta S.C. et al A role for TREM2 ligands in the phagocytosis of apoptotic neuronal cells by microglia. J. Neurochem. 2009 109 4 1144 1156 10.1111/j.1471‑4159.2009.06042.x 19302484
    [Google Scholar]
  150. Gratuze M. Leyns C.E.G. Sauerbeck A.D. et al Impact of TREM2R47H variant on tau pathology–induced gliosis and neurodegeneration. J. Clin. Invest. 2020 130 9 4954 4968 10.1172/JCI138179 32544086
    [Google Scholar]
  151. Zheng H. Cheng B. Li Y. Li X. Chen X. Zhang Y. TREM2 in Alzheimer’s disease: Microglial survival and energy metabolism. Front. Aging Neurosci. 2018 10 395 10.3389/fnagi.2018.00395 30532704
    [Google Scholar]
  152. Kang D.W. Wang S.M. Um Y.H. Kim N.Y. Lee C.U. Lim H.K. Impact of APOE ε4 carrier status on associations between subthreshold, positive amyloid-β deposition, brain function, and cognitive performance in cognitively normal older adults: A prospective study. Front. Aging Neurosci. 2022 14 871323 10.3389/fnagi.2022.871323 35677201
    [Google Scholar]
  153. Shi Y. Holtzman D.M. Interplay between innate immunity and Alzheimer disease: APOE and TREM2 in the spotlight. Nat. Rev. Immunol. 2018 18 12 759 772 10.1038/s41577‑018‑0051‑1 30140051
    [Google Scholar]
  154. Hooli B.V. Parrado A.R. Mullin K. et al The rare TREM2 R47H variant exerts only a modest effect on Alzheimer disease risk. Neurology 2014 83 15 1353 1358 10.1212/WNL.0000000000000855 25186855
    [Google Scholar]
  155. Ortega-Cubero S. Lorenzo-Betancor O. Lorenzo E. et al TREM2 R47H variant and risk of essential tremor: A cross-sectional international multicenter study. Parkinsonism Relat. Disord. 2015 21 3 306 309 10.1016/j.parkreldis.2014.12.010 25585992
    [Google Scholar]
  156. Jonsson T. Stefansson H. Steinberg S. et al Variant of TREM2 associated with the risk of Alzheimer’s disease. N. Engl. J. Med. 2013 368 2 107 116 10.1056/NEJMoa1211103 23150908
    [Google Scholar]
  157. Zajac D.J. Xu J. Cheng F. snRNA‐seq analysis of human brains suggests cell type‐specific synergistic effects of APOE4 and TREM2‐R47H and potential drug targets in Alzheimer’s Disease. Alzheimers Dement. 2024 20 S1 e092389 10.1002/alz.092389
    [Google Scholar]
  158. Del-Aguila J.L. Benitez B.A. Li Z. et al TREM2 brain transcript-specific studies in AD and TREM2 mutation carriers. Mol. Neurodegener. 2019 14 1 18 10.1186/s13024‑019‑0319‑3 31068200
    [Google Scholar]
  159. Song W. Hooli B. Mullin K. et al Alzheimer’s disease‐associated TREM2 variants exhibit either decreased or increased ligand‐dependent activation. Alzheimers Dement. 2017 13 4 381 387 10.1016/j.jalz.2016.07.004 27520774
    [Google Scholar]
  160. Park S. Mathis K.W. Lee I.K. The physiological roles of apolipoprotein J/clusterin in metabolic and cardiovascular diseases. Rev. Endocr. Metab. Disord. 2014 15 1 45 53 10.1007/s11154‑013‑9275‑3 24097125
    [Google Scholar]
  161. Laslo A. Laslo L. Arbănași E.M. et al Pathways to Alzheimer’s disease: the intersecting roles of clusterin and apolipoprotein e in amyloid-β regulation and neuronal health. Pathophysiology 2024 31 4 545 558 10.3390/pathophysiology31040040 39449522
    [Google Scholar]
  162. Harold D. Abraham R. Hollingworth P. et al Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer’s disease. Nat. Genet. 2009 41 10 1088 1093 10.1038/ng.440 19734902
    [Google Scholar]
  163. Kamboh M.I. Minster R.L. Demirci F.Y. et al Association of CLU and PICALM variants with Alzheimer’s disease. Neurobiol. Aging 2012 33 3 518 521 10.1016/j.neurobiolaging.2010.04.015 20570404
    [Google Scholar]
  164. Almeida J.F.F. dos Santos L.R. Trancozo M. de Paula F. Updated meta-analysis of BIN1, CR1, MS4A6A, CLU, and ABCA7 Variants in Alzheimer’s Disease. J. Mol. Neurosci. 2018 64 3 471 477 10.1007/s12031‑018‑1045‑y 29504051
    [Google Scholar]
  165. Han Z. Qu J. Zhao J. Zou X. Analyzing 74,248 samples confirms the association between CLU rs11136000 polymorphism and Alzheimer’s disease in caucasian but not chinese population. Sci. Rep. 2018 8 1 11062 10.1038/s41598‑018‑29450‑2 30038359
    [Google Scholar]
  166. Desikan R.S. Thompson W.K. Holland D. et al The role of clusterin in amyloid-β-associated neurodegeneration. JAMA Neurol. 2014 71 2 180 187 10.1001/jamaneurol.2013.4560 24378367
    [Google Scholar]
  167. Shepherd C.E. Affleck A.J. Bahar A.Y. Carew-Jones F. Halliday G.M. Intracellular and secreted forms of clusterin are elevated early in Alzheimer’s disease and associate with both Aβ and tau pathology. Neurobiol. Aging 2020 89 129 131 10.1016/j.neurobiolaging.2019.10.025 31813628
    [Google Scholar]
  168. Foster E.M. Dangla-Valls A. Lovestone S. Ribe E.M. Buckley N.J. Clusterin in Alzheimer’s disease: Mechanisms, genetics, and lessons from other pathologies. Front. Neurosci. 2019 13 164 10.3389/fnins.2019.00164 30872998
    [Google Scholar]
  169. Lacour A. Espinosa A. Louwersheimer E. et al Genome-wide significant risk factors for Alzheimer’s disease: Role in progression to dementia due to Alzheimer’s disease among subjects with mild cognitive impairment. Mol. Psychiatry 2017 22 1 153 160 10.1038/mp.2016.18 26976043
    [Google Scholar]
  170. Bocharova A.V. Vagaitseva K.V. Makeeva O.A. Marusin A.V. Stepanov V.A. Frequencies of alleles, genotypes and haplotypes of two polymorphisms in the clusterin gene in the Russian elderly population categorized by cognitive performance. Data Brief 2018 16 775 779 10.1016/j.dib.2017.12.019 29276745
    [Google Scholar]
  171. Serrano-Pozo A. Das S. Hyman B.T. APOE and Alzheimer’s disease: Advances in genetics, pathophysiology, and therapeutic approaches. Lancet Neurol. 2021 20 1 68 80 10.1016/S1474‑4422(20)30412‑9 33340485
    [Google Scholar]
  172. Silva M.V.F. Loures C.M.G. Alves L.C.V. de Souza L.C. Borges K.B.G. Carvalho M.G. Alzheimer’s disease: Risk factors and potentially protective measures. J. Biomed. Sci. 2019 26 1 33 10.1186/s12929‑019‑0524‑y 31072403
    [Google Scholar]
  173. Dib S. Pahnke J. Gosselet F. Role of ABCA7 in human health and in Alzheimer’s disease. Int. J. Mol. Sci. 2021 22 9 4603 10.3390/ijms22094603 33925691
    [Google Scholar]
  174. Duchateau L. Wawrzyniak N. Sleegers K. The ABC’s of Alzheimer risk gene ABCA7. Alzheimers Dement. 2024 20 5 3629 3648 10.1002/alz.13805 38556850
    [Google Scholar]
  175. Von Maydell D. Wright S. Bonner J.M. Single-cell atlas of ABCA7 loss-of-function reveals impaired neuronal respiration via choline-dependent lipid imbalances. 2023. Neuroscience 2023
    [Google Scholar]
  176. Biffi A. Anderson C.D. Desikan R.S. et al Genetic variation and neuroimaging measures in Alzheimer disease. Arch. Neurol. 2010 67 6 677 685 10.1001/archneurol.2010.108 20558387
    [Google Scholar]
  177. Liu Y. Yu J.T. Wang H.F. et al APOE genotype and neuroimaging markers of Alzheimer’s disease: Systematic review and meta-analysis. J. Neurol. Neurosurg. Psychiatry 2015 86 2 127 134 10.1136/jnnp‑2014‑307719 24838911
    [Google Scholar]
  178. Zhao Q.F. Yu J.T. Tan M.S. Tan L. ABCA7 in Alzheimer’s Disease. Mol. Neurobiol. 2015 51 3 1008 1016 10.1007/s12035‑014‑8759‑9 24878767
    [Google Scholar]
  179. Li H. Karl T. Garner B. Understanding the function of ABCA7 in Alzheimer’s disease. Biochem. Soc. Trans. 2015 43 5 920 923 10.1042/BST20150105 26517904
    [Google Scholar]
  180. Sterne J.A.C. Harbord R.M. Funnel plots in meta-analysis. Stata J. 2004 4 2 127 141 10.1177/1536867X0400400204
    [Google Scholar]
  181. Tayran H Yilmaz E Bhattarai P. ABCA7-dependent induction of neuropeptide Y is required for synaptic resilience in Alzheimer’s disease through BDNF/NGFR signaling. Cell Genom 2024 4 9
    [Google Scholar]
  182. Zhou R. Yang G. Guo X. Zhou Q. Lei J. Shi Y. Recognition of the amyloid precursor protein by human γ-secretase. Science 2019 363 6428 eaaw0930 10.1126/science.aaw0930 30630874
    [Google Scholar]
  183. Andersen O.M. Reiche J. Schmidt V. et al Neuronal sorting protein-related receptor sorLA/LR11 regulates processing of the amyloid precursor protein. Proc. Natl. Acad. Sci. USA 2005 102 38 13461 13466 10.1073/pnas.0503689102 16174740
    [Google Scholar]
  184. Andersen O.M. Schmidt V. Spoelgen R. et al Molecular dissection of the interaction between amyloid precursor protein and its neuronal trafficking receptor SorLA/LR11. Biochemistry 2006 45 8 2618 2628 10.1021/bi052120v 16489755
    [Google Scholar]
  185. Spoelgen R. von Arnim C.A.F. Thomas A.V. et al Interaction of the cytosolic domains of sorLA/LR11 with the amyloid precursor protein (APP) and β-secretase β-site APP-cleaving enzyme. J. Neurosci. 2006 26 2 418 428 10.1523/JNEUROSCI.3882‑05.2006 16407538
    [Google Scholar]
  186. Caglayan S. Takagi-Niidome S. Liao F. et al Lysosomal sorting of amyloid-β by the SORLA receptor is impaired by a familial Alzheimer’s disease mutation. Sci. Transl. Med. 2014 6 223 223ra20 10.1126/scitranslmed.3007747 24523320
    [Google Scholar]
  187. Lu X. Alzheimer’s disease’s tau and amyloid-beta hypothesis - Interplay with the innate immune system, neuroinflammation and gut microbiome 2022. China. Jinan City 2022 2511 1 020015
    [Google Scholar]
  188. Thakurta I.G. Andersen O. Associations of sorLA/SORL1 with Alzheimer’s disease. Recept Clin Investig 2015 2
    [Google Scholar]
  189. Meng Y. Lee J.H. Cheng R. St George-Hyslop P. Mayeux R. Farrer L.A. Association between SORL1 and Alzheimer’s disease in a genome-wide study. Neuroreport 2007 18 17 1761 1764 10.1097/WNR.0b013e3282f13e7a 18090307
    [Google Scholar]
  190. Kimura R. Yamamoto M. Morihara T. et al SORL1 is genetically associated with Alzheimer disease in a Japanese population. Neurosci. Lett. 2009 461 2 177 180 10.1016/j.neulet.2009.06.014 19539718
    [Google Scholar]
  191. Kölsch H. Jessen F. Wiltfang J. et al Association of SORL1 gene variants with Alzheimer’s disease. Brain Res. 2009 1264 1 6 10.1016/j.brainres.2009.01.044 19368828
    [Google Scholar]
  192. Li Y. Rowland C. Catanese J. et al SORL1 variants and risk of late-onset Alzheimer’s disease. Neurobiol. Dis. 2008 29 2 293 296 10.1016/j.nbd.2007.09.001 17949987
    [Google Scholar]
  193. Campion D. Charbonnier C. Nicolas G. SORL1 genetic variants and Alzheimer disease risk: A literature review and meta-analysis of sequencing data. Acta Neuropathol. 2019 138 2 173 186 10.1007/s00401‑019‑01991‑4 30911827
    [Google Scholar]
  194. Yin R.H. Yu J.T. Tan L. The role of SORL1 in Alzheimer’s disease. Mol. Neurobiol. 2015 51 3 909 918 10.1007/s12035‑014‑8742‑5 24833601
    [Google Scholar]
  195. Ho L. Fukuchi K. Younkin S.G. The alternatively spliced Kunitz protease inhibitor domain alters amyloid β protein precursor processing and amyloid β protein production in cultured cells. J. Biol. Chem. 1996 271 48 30929 30934 10.1074/jbc.271.48.30929 8940079
    [Google Scholar]
  196. Menéndez-González M. Pérez-Pinera P. Martínez-Rivera M. Calatayud M.T. Blázquez Menes B. APP processing and the APP-KPI domain involvement in the amyloid cascade. Neurodegener. Dis. 2005 2 6 277 283 10.1159/000092315 16909010
    [Google Scholar]
  197. Bauer C. Duplan E. Saint-George-Hyslop P. Checler F. Potentially pathogenic SORL1 mutations observed in autosomal-dominant cases of Alzheimer’s disease do not modulate APP physiopathological processing. Cells 2023 12 24 2802 10.3390/cells12242802 38132122
    [Google Scholar]
  198. Mockett B.G. Richter M. Abraham W.C. Müller U.C. Therapeutic potential of secreted amyloid precursor protein APPsα. Front. Mol. Neurosci. 2017 10 30 10.3389/fnmol.2017.00030 28223920
    [Google Scholar]
  199. De Roeck A. Van Broeckhoven C. Sleegers K. The role of ABCA7 in Alzheimer’s disease: Evidence from genomics, transcriptomics and methylomics. Acta Neuropathol. 2019 138 2 201 220 10.1007/s00401‑019‑01994‑1 30903345
    [Google Scholar]
  200. Aikawa T. Holm M.L. Kanekiyo T. ABCA7 and Pathogenic Pathways of Alzheimer’s Disease. Brain Sci. 2018 8 2 27 10.3390/brainsci8020027 29401741
    [Google Scholar]
  201. Oblak A.L. Kotredes K.P. Ingraham C. et al The role of Abca7 in late‐onset Alzheimer’s disease animal models. Alzheimers Dement. 2022 18 S3 e067665 10.1002/alz.067665
    [Google Scholar]
  202. Pereira C.D. Martins F. Wiltfang J. da Cruz e Silva OAB, Rebelo S. ABC transporters are key players in Alzheimer’s disease. J. Alzheimers Dis. 2017 61 2 463 485 10.3233/JAD‑170639 29171999
    [Google Scholar]
  203. Malik M. Parikh I. Vasquez J.B. et al Genetics ignite focus on microglial inflammation in Alzheimer’s disease. Mol. Neurodegener. 2015 10 1 52 10.1186/s13024‑015‑0048‑1 26438529
    [Google Scholar]
  204. Suárez-Calvet M. Karikari T.K. Ashton N.J. et al Novel tau biomarkers phosphorylated at T181, T217 or T231 rise in the initial stages of the preclinical Alzheimer’s continuum when only subtle changes in Aβ pathology are detected. EMBO Mol. Med. 2020 12 12 e12921 10.15252/emmm.202012921 33169916
    [Google Scholar]
  205. Lamartinière Y. Boucau M.C. Dehouck L. et al ABCA7 downregulation modifies cellular cholesterol homeostasis and decreases amyloid-β peptide efflux in an in vitro model of the blood-brain barrier. J. Alzheimers Dis. 2018 64 4 1195 1211 10.3233/JAD‑170883 30010117
    [Google Scholar]
  206. Hartmann C. Jung M. Ehrhardt T. Giegling I. Rujescu D. Establishing a blood-brain barrier model for the analysis of Alzheimer’s disease using patient derived induced pluripotent stem cells. Eur. Neuropsychopharmacol. 2019 29 S904 10.1016/j.euroneuro.2017.08.220
    [Google Scholar]
  207. Apostolova L.G. Risacher S.L. Duran T. et al Associations of the top 20 Alzheimer disease risk variants with brain amyloidosis. JAMA Neurol. 2018 75 3 328 341 10.1001/jamaneurol.2017.4198 29340569
    [Google Scholar]
  208. Aikawa T. Ren Y. Yamazaki Y. et al ABCA7 haplodeficiency disturbs microglial immune responses in the mouse brain. Proc. Natl. Acad. Sci. USA 2019 116 47 23790 23796 10.1073/pnas.1908529116 31690660
    [Google Scholar]
  209. Duchateau L. Küҫükali F. De Roeck A. et al CSF biomarker analysis of ABCA7 mutation carriers suggests altered APP processing and reduced inflammatory response. Alzheimers Res. Ther. 2023 15 1 195 10.1186/s13195‑023‑01338‑y 37946268
    [Google Scholar]
  210. Dong L. Mao C. Liu C. et al Association between common variants of APOE, ABCA7, A2M, BACE1, and cerebrospinal fluid biomarkers in Alzheimer’s disease: Data from the PUMCH dementia cohort. J. Alzheimers Dis. 2022 85 4 1511 1518 10.3233/JAD‑215067 34958020
    [Google Scholar]
  211. Howell G.R. Kotredes K.P. Pandey R.S. et al Elucidating the complex role of ABCA7 in late‐onset Alzheimer’s disease. Alzheimers Dement. 2023 19 S12 e078038 10.1002/alz.078038
    [Google Scholar]
  212. Wray N.R. Goddard M.E. Visscher P.M. Prediction of individual genetic risk to disease from genome-wide association studies. Genome Res. 2007 17 10 1520 1528 10.1101/gr.6665407 17785532
    [Google Scholar]
  213. Conomos M.P. Laurie C.A. Stilp A.M. et al Genetic diversity and association studies in US hispanic/latino populations: Applications in the hispanic community health study/study of latinos. Am. J. Hum. Genet. 2016 98 1 165 184 10.1016/j.ajhg.2015.12.001 26748518
    [Google Scholar]
  214. Lambert J-C F1–01–01: Meta-analysis in more than 74,000 individuals identifies 11 new susceptibility loci for Alzheimer’s disease. Alzheimers Dement. 2013 9 4S_Part_3 123 3
    [Google Scholar]
  215. Romero-Rosales B.L. Tamez-Pena J.G. Nicolini H. Moreno-Treviño M.G. Trevino V. Improving predictive models for Alzheimer’s disease using GWAS data by incorporating misclassified samples modeling. PLoS One 2020 15 4 e0232103 10.1371/journal.pone.0232103 32324812
    [Google Scholar]
  216. Escott-Price V. Hardy J. Genome-wide association studies for Alzheimer’s disease: Bigger is not always better. Brain Commun. 2022 4 3 fcac125 10.1093/braincomms/fcac125 35663382
    [Google Scholar]
  217. Shen L. Jia J. An overview of genome-wide association studies in Alzheimer’s disease. Neurosci. Bull. 2016 32 2 183 190 10.1007/s12264‑016‑0011‑3 26810783
    [Google Scholar]
  218. Gao S. Wang T. Han Z. et al Interpretation of 10 years of Alzheimer’s disease genetic findings in the perspective of statistical heterogeneity. Brief. Bioinform. 2024 25 3 bbae140 10.1093/bib/bbae140 38711368
    [Google Scholar]
  219. Bentley A.R. Callier S. Rotimi C.N. Diversity and inclusion in genomic research: Why the uneven progress? J. Community Genet. 2017 8 4 255 266 10.1007/s12687‑017‑0316‑6 28770442
    [Google Scholar]
  220. Kim M.S. Patel K.P. Teng A.K. Berens A.J. Lachance J. Genetic disease risks can be misestimated across global populations. Genome Biol. 2018 19 1 179 10.1186/s13059‑018‑1561‑7 30424772
    [Google Scholar]
  221. Bertram L. Tanzi R.E. Genome-wide association studies in Alzheimer’s disease. Hum. Mol. Genet. 2009 18 R2 R137 R145 10.1093/hmg/ddp406 19808789
    [Google Scholar]
  222. Jung Y.J. Kim Y.H. Bhalla M. Lee S.B. Seo J. Genomics: New Light on Alzheimer’s Disease Research. Int. J. Mol. Sci. 2018 19 12 3771 10.3390/ijms19123771 30486438
    [Google Scholar]
  223. Borovecki F. Klepac N. Muck-Seler D. Hajnsek S. Mubrin Z. Pivac N. Unraveling the biological mechanisms in Alzheimer’s disease — Lessons from genomics. Prog. Neuropsychopharmacol. Biol. Psychiatry 2011 35 2 340 347 10.1016/j.pnpbp.2010.12.019 21193006
    [Google Scholar]
  224. Singh M.K. Shin Y. Ju S. Han S. Kim S.S. Kang I. Comprehensive overview of Alzheimer’s disease: Etiological insights and degradation strategies. Int. J. Mol. Sci. 2024 25 13 6901 10.3390/ijms25136901 39000011
    [Google Scholar]
  225. Moraes C.F. Lins T.C. Carmargos E.F. Naves J.O.S. Pereira R.W. Nóbrega O.T. Lessons from genome‐wide association studies findings in Alzheimer’s disease. Psychogeriatrics 2012 12 1 62 73 10.1111/j.1479‑8301.2011.00378.x 22416831
    [Google Scholar]
  226. Rosenberg N.A. Huang L. Jewett E.M. Szpiech Z.A. Jankovic I. Boehnke M. Genome-wide association studies in diverse populations. Nat. Rev. Genet. 2010 11 5 356 366 10.1038/nrg2760 20395969
    [Google Scholar]
  227. Dehghani N. Bras J. Guerreiro R. How understudied populations leverage our understanding of Alzheimer’s disease genetics. Alzheimers Dement. 2020 16 S2 e044901 10.1002/alz.044901
    [Google Scholar]
  228. Edland S.D. Slager S. Farrer M. Genetic association studies in Alzheimer’s disease research: Challenges and opportunities. Stat. Med. 2004 23 2 169 178 10.1002/sim.1706 14716719
    [Google Scholar]
  229. Bertram L. Tanzi R.E. Alzheimer’s disease: One disorder, too many genes? Hum. Mol. Genet. 2004 13 90001 135R 41 10.1093/hmg/ddh077 14764623
    [Google Scholar]
  230. Cruchaga C. Karch C.M. Jin S.C. et al Rare coding variants in the phospholipase D3 gene confer risk for Alzheimer’s disease. Nature 2014 505 7484 550 554 10.1038/nature12825 24336208
    [Google Scholar]
  231. Tosto G. Fu H. Vardarajan B.N. et al F‐box/LRR ‐repeat protein 7 is genetically associated with Alzheimer’s disease. Ann. Clin. Transl. Neurol. 2015 2 8 810 820 10.1002/acn3.223 26339675
    [Google Scholar]
  232. Herold C. Hooli B.V. Mullin K. et al Family-based association analyses of imputed genotypes reveal genome-wide significant association of Alzheimer’s disease with OSBPL6, PTPRG, and PDCL3. Mol. Psychiatry 2016 21 11 1608 1612 10.1038/mp.2015.218 26830138
    [Google Scholar]
  233. Mez J. Chung J. Jun G. et al Two novel loci, COBL and SLC10A2, for Alzheimer’s disease in African Americans. Alzheimers Dement. 2017 13 2 119 129 10.1016/j.jalz.2016.09.002 27770636
    [Google Scholar]
  234. Hao S. Wang R. Zhang Y. Zhan H. Prediction of Alzheimer’s disease-associated genes by integration of GWAS summary data and expression data. Front. Genet. 2019 9 653 10.3389/fgene.2018.00653 30666269
    [Google Scholar]
  235. Kunkle B.W. Schmidt M. Klein H.U. et al Novel Alzheimer disease risk loci and pathways in African American individuals using the African genome resources panel. JAMA Neurol. 2021 78 1 102 113 10.1001/jamaneurol.2020.3536 33074286
    [Google Scholar]
  236. Schwartzentruber J. Cooper S. Liu J.Z. et al Genome-wide meta-analysis, fine-mapping and integrative prioritization implicate new Alzheimer’s disease risk genes. Nat. Genet. 2021 53 3 392 402 10.1038/s41588‑020‑00776‑w 33589840
    [Google Scholar]
  237. Shigemizu D. Asanomi Y. Akiyama S. Mitsumori R. Niida S. Ozaki K. Whole-genome sequencing reveals novel ethnicity-specific rare variants associated with Alzheimer’s disease. Mol. Psychiatry 2022 27 5 2554 2562 10.1038/s41380‑022‑01483‑0 35264725
    [Google Scholar]
  238. Bellenguez C. Küçükali F. Jansen I.E. et al New insights into the genetic etiology of Alzheimer’s disease and related dementias. Nat. Genet. 2022 54 4 412 436 10.1038/s41588‑022‑01024‑z 35379992
    [Google Scholar]
  239. Ar P Fernandes Gf DS Jl DS Clinical pharmacology: Epigenetic drugs at a glance. Biochem Pharmacol Open Access 2018 7 2
    [Google Scholar]
  240. Kanherkar R.R. Bhatia-Dey N. Csoka A.B. Epigenetics across the human lifespan. Front. Cell Dev. Biol. 2014 2 49 10.3389/fcell.2014.00049 25364756
    [Google Scholar]
  241. De Plano L.M. Saitta A. Oddo S. Caccamo A. Epigenetic changes in Alzheimer’s disease: DNA methylation and histone modification. Cells 2024 13 8 719 10.3390/cells13080719 38667333
    [Google Scholar]
  242. Wood I.C. The contribution and therapeutic potential of epigenetic modifications in Alzheimer’s disease. Front. Neurosci. 2018 12 649 10.3389/fnins.2018.00649 30283297
    [Google Scholar]
  243. Marzi S.J. Leung S.K. Ribarska T. et al A histone acetylome-wide association study of Alzheimer’s disease identifies disease-associated H3K27ac differences in the entorhinal cortex. Nat. Neurosci. 2018 21 11 1618 1627 10.1038/s41593‑018‑0253‑7 30349106
    [Google Scholar]
  244. Zusso M. Barbierato M. Facci L. Skaper S.D. Giusti P. Neuroepigenetics and Alzheimer’s disease: An Update. J. Alzheimers Dis. 2018 64 3 671 688 10.3233/JAD‑180259 29991138
    [Google Scholar]
  245. Rahman M.R. Islam T. Gov E. Quinn J.M.W. Moni M.A. Identifying the function of methylated genes in Alzheimer’s disease to determine epigenetic signatures: A comprehensive bioinformatics analysis. Experimental Results 2021 2 e9 10.1017/exp.2020.65
    [Google Scholar]
  246. Watson C.T. Roussos P. Garg P. et al Genome-wide DNA methylation profiling in the superior temporal gyrus reveals epigenetic signatures associated with Alzheimer’s disease. Genome Med. 2016 8 1 5 10.1186/s13073‑015‑0258‑8 26803900
    [Google Scholar]
  247. Rubio-Perez J.M. Morillas-Ruiz J.M. A review: Inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012 2012 1 15 10.1100/2012/756357 22566778
    [Google Scholar]
  248. Nikolac Perkovic M. Videtic Paska A. Konjevod M. et al Epigenetics of Alzheimer’s Disease. Biomolecules 2021 11 2 195 10.3390/biom11020195 33573255
    [Google Scholar]
  249. Liu X. Jiao B. Shen L. The epigenetics of Alzheimer’s disease: Factors and therapeutic implications. Front. Genet. 2018 9 579 10.3389/fgene.2018.00579 30555513
    [Google Scholar]
  250. Adwan L. Zawia N.H. Epigenetics: A novel therapeutic approach for the treatment of Alzheimer’s disease. Pharmacol. Ther. 2013 139 1 41 50 10.1016/j.pharmthera.2013.03.010 23562602
    [Google Scholar]
  251. Cacabelos R. Torrellas C. Epigenetic drug discovery for Alzheimer’s disease. Expert Opin. Drug Discov. 2014 9 9 1059 1086 10.1517/17460441.2014.930124 24989365
    [Google Scholar]
  252. Hersi M. Irvine B. Gupta P. Gomes J. Birkett N. Krewski D. Risk factors associated with the onset and progression of Alzheimer’s disease: A systematic review of the evidence. Neurotoxicology 2017 61 143 187 10.1016/j.neuro.2017.03.006 28363508
    [Google Scholar]
  253. Karlsson I.K. Escott-Price V. Gatz M. et al Measuring heritable contributions to Alzheimer’s disease: Polygenic risk score analysis with twins. Brain Commun. 2022 4 1 fcab308 10.1093/braincomms/fcab308 35169705
    [Google Scholar]
  254. Yegambaram M. Manivannan B. Beach T. Halden R. Role of environmental contaminants in the etiology of Alzheimer’s disease: A review. Curr. Alzheimer Res. 2015 12 2 116 146 10.2174/1567205012666150204121719 25654508
    [Google Scholar]
  255. Ni H. Xu M. Zhan G.L. et al The GWAS risk genes for depression may be actively involved in Alzheimer’s disease. J. Alzheimers Dis. 2018 64 4 1149 1161 10.3233/JAD‑180276 30010129
    [Google Scholar]
  256. Eid A. Mhatre I. Richardson J.R. Gene-environment interactions in Alzheimer’s disease: A potential path to precision medicine. Pharmacol. Ther. 2019 199 173 187 10.1016/j.pharmthera.2019.03.005 30877021
    [Google Scholar]
  257. Seifan A. Schelke M. Obeng-Aduasare Y. Isaacson R. Early life epidemiology of Alzheimer’s disease - A critical review. Neuroepidemiology 2015 45 4 237 254 10.1159/000439568 26501691
    [Google Scholar]
  258. Belleville S. Fouquet C. Hudon C. Zomahoun H.T.V. Croteau J. Neuropsychological measures that predict progression from mild cognitive impairment to Alzheimer’s type dementia in older adults: A systematic review and meta-analysis. Neuropsychol. Rev. 2017 27 4 328 353 10.1007/s11065‑017‑9361‑5 29019061
    [Google Scholar]
  259. Yamazaki Y. Painter M.M. Bu G. Kanekiyo T. Apolipoprotein E as a therapeutic target in Alzheimer’s disease: A review of basic research and clinical evidence. CNS Drugs 2016 30 9 773 789 10.1007/s40263‑016‑0361‑4 27328687
    [Google Scholar]
  260. Williams V Trane R Sicinski K Herd P Engleman M Asthana S Mid-life and late-life environmental exposures on dementia risk: the modifying effects of apoe. Innov Aging 2024 8 417 7 10.1093/geroni/igae098.1358
    [Google Scholar]
  261. Lakomski NA Giorgio K Stephen J et al Abstract P330: The association between APOE genotype and dementia in the dementia risk pooling project. Circulation 2024 149 AP330 0 10.1161/circ.149.suppl_1.P330
    [Google Scholar]
  262. Dempfle A. Scherag A. Hein R. Beckmann L. Chang-Claude J. Schäfer H. Gene–environment interactions for complex traits: Definitions, methodological requirements and challenges. Eur. J. Hum. Genet. 2008 16 10 1164 1172 10.1038/ejhg.2008.106 18523454
    [Google Scholar]
  263. Dick D.M. Agrawal A. Keller M.C. et al Candidate gene-environment interaction research: Reflections and recommendations. Perspect. Psychol. Sci. 2015 10 1 37 59 10.1177/1745691614556682 25620996
    [Google Scholar]
  264. Weaver I.C.G. Shaping adult phenotypes through early life environments. Birth Defects Res. C Embryo Today 2009 87 4 314 326 10.1002/bdrc.20164 19960543
    [Google Scholar]
  265. Hampel H. Nisticò R. Seyfried N.T. et al Omics sciences for systems biology in Alzheimer’s disease: State-of-the-art of the evidence. Ageing Res. Rev. 2021 69 101346 10.1016/j.arr.2021.101346 33915266
    [Google Scholar]
  266. Guzman-Martinez L. Calfío C. Farias G.A. Vilches C. Prieto R. Maccioni R.B. New frontiers in the prevention, diagnosis, and treatment of Alzheimer’s disease. J. Alzheimers Dis. 2021 82 s1 S51 S63 10.3233/JAD‑201059 33523002
    [Google Scholar]
  267. Cacabelos R. Pharmacogenomics for the treatment of dementia. Ann. Med. 2002 34 5 357 379 10.1080/078538902320772115 12452480
    [Google Scholar]
  268. Sumirtanurdin R. Thalib A.Y. Cantona K. Abdulah R. Effect of genetic polymorphisms on Alzheimer’s disease treatment outcomes: An update. Clin. Interv. Aging 2019 14 631 642 10.2147/CIA.S200109 30992661
    [Google Scholar]
  269. Kamboh M.I. Genomics and functional genomics of Alzheimer’s disease. Neurotherapeutics 2022 19 1 152 172 10.1007/s13311‑021‑01152‑0 34935119
    [Google Scholar]
  270. Ringman J.M. Goate A. Masters C.L. et al Genetic heterogeneity in Alzheimer disease and implications for treatment strategies. Curr. Neurol. Neurosci. Rep. 2014 14 11 499 10.1007/s11910‑014‑0499‑8 25217249
    [Google Scholar]
  271. Caselli RJ Reiman EM Characterizing the preclinical stages of Alzheimer’s disease and the prospect of presymptomatic intervention. J Alzheimers Dis 2013 33 0 1 S405 16 (Suppl. 1) 22695623
    [Google Scholar]
  272. Langbaum J.B. Fleisher A.S. Chen K. et al Ushering in the study and treatment of preclinical Alzheimer disease. Nat. Rev. Neurol. 2013 9 7 371 381 10.1038/nrneurol.2013.107 23752908
    [Google Scholar]
  273. Wolfe C.M. Fitz N.F. Nam K.N. Lefterov I. Koldamova R. The role of APOE and TREM2 in Alzheimer′s disease—Current understanding and perspectives. Int. J. Mol. Sci. 2018 20 1 81 10.3390/ijms20010081 30587772
    [Google Scholar]
  274. Long H. Simmons A. Mayorga A. et al Preclinical and first-in-human evaluation of AL002, a novel TREM2 agonistic antibody for Alzheimer’s disease. Alzheimers Res. Ther. 2024 16 1 235 10.1186/s13195‑024‑01599‑1 39444037
    [Google Scholar]
  275. Yang A. Kantor B. Chiba-Falek O. APOE: The new frontier in the development of a therapeutic target towards precision medicine in late-onset Alzheimer’s. Int. J. Mol. Sci. 2021 22 3 1244 10.3390/ijms22031244 33513969
    [Google Scholar]
  276. Grabowska-Pyrzewicz W. Want A. Leszek J. Wojda U. Antisense oligonucleotides for Alzheimer’s disease therapy: From the mRNA to miRNA paradigm. EBioMedicine 2021 74 103691 10.1016/j.ebiom.2021.103691 34773891
    [Google Scholar]
  277. Deming Y. Li Z. Benitez B.A. Cruchaga C. Triggering receptor expressed on myeloid cells 2 (TREM2): A potential therapeutic target for Alzheimer disease? Expert Opin. Ther. Targets 2018 22 7 587 598 10.1080/14728222.2018.1486823 29889572
    [Google Scholar]
  278. Mohan S.V. Freedman J. A review of the evolving landscape of inclusive research and improved clinical trial access. Clin. Pharmacol. Ther. 2023 113 3 518 527 10.1002/cpt.2832 36536992
    [Google Scholar]
  279. Zhu S. Genetic insights and predictive models in Alzheimer’s disease. Transactions on Materials. Biotechnology and Life Sciences 2024 7 497 506 10.62051/bsh2zw61
    [Google Scholar]
  280. Ramanan V.K. Gebre R.K. Graff-Radford J. et al Genetic risk scores enhance the diagnostic value of plasma biomarkers of brain amyloidosis. Brain 2023 146 11 4508 4519 10.1093/brain/awad196 37279785
    [Google Scholar]
  281. Bhat R. Varshini V. Himasvi H. Shabaraya R. Pharmacogenomic approaches in Alzheimer’s disease: A comprehensive review. Int J Pharm Phytopharma Res 2023 13 4 7 13 10.51847/qDMSgl63u7
    [Google Scholar]
  282. Saragea P.D. Alzheimer’s disease (AD): Environmental modifiable risk factors. Int J Multidiscip Res IJFMR 2024 6 4
    [Google Scholar]
  283. Rentería M.E. Mitchell B.L. de Lara A.M. Genetic testing for Alzheimer’s disease: Trends, challenges and ethical considerations. Curr. Opin. Psychiatry 2020 33 2 136 140 10.1097/YCO.0000000000000573 31770136
    [Google Scholar]
  284. Baker E. Escott-Price V. Polygenic risk scores in Alzheimer’s disease: Current applications and future directions. Frontiers in Digital Health 2020 2 14 10.3389/fdgth.2020.00014 34713027
    [Google Scholar]
  285. Reitz C. Toward precision medicine in Alzheimer’s disease. Ann. Transl. Med. 2016 4 6 107 7 10.21037/atm.2016.03.05 27127760
    [Google Scholar]
  286. Forloni G. Alzheimer’s disease: From basic science to precision medicine approach. BMJ Neurology Open 2020 2 2 e000079 10.1136/bmjno‑2020‑000079 33681801
    [Google Scholar]
/content/journals/cgt/10.2174/0115665232397101250916050247
Loading
A Comprehensive Review of Genetic Risk Factors for Alzheimer’s Disease Development
Bentham Science Publishers ; https://doi.org/10.2174/0115665232397101250916050247
/content/journals/cgt/10.2174/0115665232397101250916050247
/content/journals/cgt/10.2174/0115665232397101250916050247
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: epigenetics ; genetic risk factors ; GWAS ; ABCA7 ; APOE ; TREM2 ; SORL1 ; Alzheimer’s disease

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test