Skip to content
2000
Volume 22, Issue 3
  • ISSN: 1567-2050
  • E-ISSN: 1875-5828

Abstract

Social isolation (SI) and loneliness (perceived social isolation) are considered as risk factors for developing dementia, including Alzheimer’s disease (AD), in the elderly population. Intriguingly, recent reports have shown a significant association of loneliness with a higher amyloid-β (Aβ) burden, suggesting that SI is linked to the pathophysiology of AD. Numerous studies, using rodents or other animal models have revealed diverse biological effects of SI, including induction of oxidative stress and activation of neuroinflammation. Furthermore, using transgenic mouse models of AD, recent investigations have shown that SI affects AD pathology, particularly the deposition of Aβ and neuroinflammation. However, it remains unclarified, by which mechanisms SI confers a significant risk for AD. In this narrative mini-review, I overview published studies on the pathobiological effects of SI in rodent models and discuss the mechanisms by which SI exacerbates AD pathology. Clarification of this issue has significant implications for the design of strategies for preventing cognitive impairment and dementia in the elderly population.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/car/10.2174/0115672050373522250421054927
2025-04-28
2025-10-23

  • From This Site

    /content/journals/car/10.2174/0115672050373522250421054927
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. LiuY. ZhaoH. LiQ. CuiH. HuangG. Research progress on the etiology and pathogenesis of Alzheimer’s disease from the perspective of chronic stress.Aging Dis.20221441292-131010.14336/AD.2022.121137163426
     [Google Scholar]
  2. FriedlerB. CrapserJ. McCulloughL. One is the deadliest number: The detrimental effects of social isolation on cerebrovascular diseases and cognition.Acta Neuropathol.2015129449350910.1007/s00401‑014‑1377‑925537401
     [Google Scholar]
  3. LivingstonG. HuntleyJ. SommerladA. AmesD. BallardC. BanerjeeS. BrayneC. BurnsA. Cohen-MansfieldJ. CooperC. CostafredaS.G. DiasA. FoxN. GitlinL.N. HowardR. KalesH.C. KivimäkiM. LarsonE.B. OgunniyiA. OrgetaV. RitchieK. RockwoodK. SampsonE.L. SamusQ. SchneiderL.S. SelbækG. TeriL. MukadamN. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission.Lancet20203961024841344610.1016/S0140‑6736(20)30367‑632738937
     [Google Scholar]
  4. LivingstonG. HuntleyJ. LiuK.Y. CostafredaS.G. SelbækG. AlladiS. AmesD. BanerjeeS. BurnsA. BrayneC. FoxN.C. FerriC.P. GitlinL.N. HowardR. KalesH.C. KivimäkiM. LarsonE.B. NakasujjaN. RockwoodK. SamusQ. ShiraiK. Singh-ManouxA. SchneiderL.S. WalshS. YaoY. SommerladA. MukadamN. Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission.Lancet20244041045257262810.1016/S0140‑6736(24)01296‑039096926
     [Google Scholar]
  5. GuarneraJ. YuenE. MacphersonH. The impact of loneliness and social isolation on cognitive aging: A narrative review.J. Alzheimers Dis. Rep.20237169971410.3233/ADR‑23001137483321
     [Google Scholar]
  6. RenY. SavadlouA. ParkS. SiskaP. EppJ.R. SarginD. The impact of loneliness and social isolation on the development of cognitive decline and Alzheimer’s Disease.Front. Neuroendocrinol.20236910106110.1016/j.yfrne.2023.10106136758770
     [Google Scholar]
  7. SperlingR.A. AisenP.S. BeckettL.A. BennettD.A. CraftS. FaganA.M. IwatsuboT. JackC.R.Jr KayeJ. MontineT.J. ParkD.C. ReimanE.M. RoweC.C. SiemersE. SternY. YaffeK. CarrilloM.C. ThiesB. Morrison-BogoradM. WagsterM.V. PhelpsC.H. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease.Alzheimers Dement.20117328029210.1016/j.jalz.2011.03.00321514248
     [Google Scholar]
  8. Serrano-PozoA. FroschM.P. MasliahE. HymanB.T. Neuropathological alterations in Alzheimer disease.Cold Spring Harb. Perspect. Med.201111a00618910.1101/cshperspect.a00618922229116
     [Google Scholar]
  9. De StrooperB. VassarR. GoldeT. The secretases: Enzymes with therapeutic potential in Alzheimer disease.Nat. Rev. Neurol.2010629910710.1038/nrneurol.2009.21820139999
     [Google Scholar]
  10. HampelH. HardyJ. BlennowK. ChenC. PerryG. KimS.H. VillemagneV.L. AisenP. VendruscoloM. IwatsuboT. MastersC.L. ChoM. LannfeltL. CummingsJ.L. VergalloA. The Amyloid-β pathway in Alzheimer’s disease.Mol. Psychiatry202126105481550310.1038/s41380‑021‑01249‑034456336
     [Google Scholar]
  11. OnoK. TsujiM. Protofibrils of Amyloid-β are important targets of a disease-modifying approach for Alzheimer’s disease.Int. J. Mol. Sci.202021395210.3390/ijms2103095232023927
     [Google Scholar]
  12. ArakiW. Aβ oligomer toxicity-reducing therapy for the prevention of Alzheimer's disease: Importance of the Nrf2 and PPARγ pathways.Cells20231210138610.3390/cells1210138637408220
     [Google Scholar]
  13. TuckerS. MöllerC. TegerstedtK. LordA. LaudonH. SjödahlJ. SöderbergL. SpensE. SahlinC. WaaraE.R. SatlinA. GellerforsP. OsswaldG. LannfeltL. The murine version of BAN2401 (mAb158) selectively reduces amyloid-β protofibrils in brain and cerebrospinal fluid of tg-ArcSwe mice.J. Alzheimers Dis.201443257558810.3233/JAD‑14074125096615
     [Google Scholar]
  14. van DyckC.H. SwansonC.J. AisenP. BatemanR.J. ChenC. GeeM. KanekiyoM. LiD. ReydermanL. CohenS. FroelichL. KatayamaS. SabbaghM. VellasB. WatsonD. DhaddaS. IrizarryM. KramerL.D. IwatsuboT. Lecanemab in early Alzheimer’s disease.N. Engl. J. Med.2023388192110.1056/NEJMoa221294836449413
     [Google Scholar]
  15. HenekaM.T. CarsonM.J. KhouryJ.E. LandrethG.E. BrosseronF. FeinsteinD.L. JacobsA.H. Wyss-CorayT. VitoricaJ. RansohoffR.M. HerrupK. FrautschyS.A. FinsenB. BrownG.C. VerkhratskyA. YamanakaK. KoistinahoJ. LatzE. HalleA. PetzoldG.C. TownT. MorganD. ShinoharaM.L. PerryV.H. HolmesC. BazanN.G. BrooksD.J. HunotS. JosephB. DeigendeschN. GaraschukO. BoddekeE. DinarelloC.A. BreitnerJ.C. ColeG.M. GolenbockD.T. KummerM.P. Neuroinflammation in Alzheimer’s disease.Lancet Neurol.201514438840510.1016/S1474‑4422(15)70016‑525792098
     [Google Scholar]
  16. KinneyJ.W. BemillerS.M. MurtishawA.S. LeisgangA.M. SalazarA.M. LambB.T. Inflammation as a central mechanism in Alzheimer’s disease.Alzheimers Dement.20184157559010.1016/j.trci.2018.06.01430406177
     [Google Scholar]
  17. DansokhoC. HenekaM.T. Neuroinflammatory responses in Alzheimer’s disease.J. Neural Transm.2018125577177910.1007/s00702‑017‑1831‑729273951
     [Google Scholar]
  18. KuiperJ.S. ZuidersmaM. Oude VoshaarR.C. ZuidemaS.U. van den HeuvelE.R. StolkR.P. SmidtN. Social relationships and risk of dementia: A systematic review and meta-analysis of longitudinal cohort studies.Ageing Res. Rev.201522395710.1016/j.arr.2015.04.00625956016
     [Google Scholar]
  19. PenninkilampiR. CaseyA.N. SinghM.F. BrodatyH. The association between social engagement, loneliness, and risk of dementia: A systematic review and meta-analysis.J. Alzheimers Dis.20186641619163310.3233/JAD‑18043930452410
     [Google Scholar]
  20. WilsonR.S. KruegerK.R. ArnoldS.E. SchneiderJ.A. KellyJ.F. BarnesL.L. TangY. BennettD.A. Loneliness and risk of Alzheimer disease.Arch. Gen. Psychiatry200764223424010.1001/archpsyc.64.2.23417283291
     [Google Scholar]
  21. WilsonR.S. CapuanoA.W. SampaioC. The link between social and emotional isolation and dementia in older black and white Brazilians.Int. Psychogeriatr.20211710.1017/S104161022100067334127171
     [Google Scholar]
  22. ShenC. RollsE.T. ChengW. KangJ. DongG. XieC. ZhaoX.M. SahakianB.J. FengJ. Associations of social isolation and loneliness with later dementia.Neurology2022992e164e17510.1212/WNL.000000000020058335676089
     [Google Scholar]
  23. GroechelR.C. LiuA.C. LiuC. KnopmanD.S. KotonS. Kucharska-NewtonA.M. LutseyP.L. MosleyT.H.Jr PaltaP. SharrettA.R. WalkerK.A. WongD.F. GottesmanR.F. Social relationships, amyloid burden, and dementia: The ARIC-PET study.Alzheimers Dement.2024162e1256010.1002/dad2.1256038571965
     [Google Scholar]
  24. SommerladA. KivimäkiM. LarsonE.B. RöhrS. ShiraiK. Singh-ManouxA. LivingstonG. Social participation and risk of developing dementia.Nat. Aging20233553254510.1038/s43587‑023‑00387‑037202513
     [Google Scholar]
  25. JoshiP. HendrieK. JesterD.J. DasarathyD. LavretskyH. KuB.S. LeutwylerH. TorousJ. JesteD.V. TampiR.R. Social connections as determinants of cognitive health and as targets for social interventions in persons with or at risk of Alzheimer’s disease and related disorders: A scoping review.Int. Psychogeriatr.20243629211810.1017/S104161022300092337994532
     [Google Scholar]
  26. DonovanN.J. OkerekeO.I. VanniniP. AmariglioR.E. RentzD.M. MarshallG.A. JohnsonK.A. SperlingR.A. Association of higher cortical amyloid burden with loneliness in cognitively normal older adults.JAMA Psychiatry201673121230123710.1001/jamapsychiatry.2016.265727806159
     [Google Scholar]
  27. Kehrer-DunlapA. BollingerR. ChenS.W. KelemanA. ThompsonR. FaganA. AncesB. StarkS. Higher amyloid is associated with greater loneliness among cognitively normal older adults during the COVID-19 pandemic.F1000 Res.202211113410.12688/f1000research.124891.239434871
     [Google Scholar]
  28. d’Oleire UquillasF. JacobsH.I.L. BiddleK.D. ProperziM. HanseeuwB. SchultzA.P. RentzD.M. JohnsonK.A. SperlingR.A. DonovanN.J. Regional tau pathology and loneliness in cognitively normal older adults.Transl. Psychiatry20188128210.1038/s41398‑018‑0345‑x30563962
     [Google Scholar]
  29. MumtazF. KhanM.I. ZubairM. DehpourA.R. Neurobiology and consequences of social isolation stress in animal model—A comprehensive review.Biomed. Pharmacother.20181051205122210.1016/j.biopha.2018.05.08630021357
     [Google Scholar]
  30. FilipovićD. TodorovićN. BernardiR.E. GassP. Oxidative and nitrosative stress pathways in the brain of socially isolated adult male rats demonstrating depressive- and anxiety-like symptoms.Brain Struct. Funct.2017222112010.1007/s00429‑016‑1218‑927033097
     [Google Scholar]
  31. CacioppoJ.T. CacioppoS. CapitanioJ.P. ColeS.W. The neuroendocrinology of social isolation.Annu. Rev. Psychol.201566173376710.1146/annurev‑psych‑010814‑01524025148851
     [Google Scholar]
  32. ZorrillaE.P. LogripM.L. KoobG.F. Corticotropin releasing factor: A key role in the neurobiology of addiction.Front. Neuroendocrinol.201435223424410.1016/j.yfrne.2014.01.00124456850
     [Google Scholar]
  33. HostetlerC.M. RyabininA.E. The CRF system and social behavior: A review.Front. Neurosci.201379210.3389/fnins.2013.0009223754975
     [Google Scholar]
  34. SchiavoneS. SorceS. Dubois-DauphinM. JaquetV. ColaiannaM. ZottiM. CuomoV. TrabaceL. KrauseK.H. Involvement of NOX2 in the development of behavioral and pathologic alterations in isolated rats.Biol. Psychiatry200966438439210.1016/j.biopsych.2009.04.03319559404
     [Google Scholar]
  35. Al OmranA.J. WatanabeS. HongE.C. SkinnerS.G. ZhangM. ZhangJ. ShaoX.M. LiangJ. Dihydromyricetin ameliorates social isolation-induced anxiety by modulating mitochondrial function, antioxidant enzymes, and BDNF.Neurobiol. Stress20222110049910.1016/j.ynstr.2022.10049936532369
     [Google Scholar]
  36. GongW.G. WangY.J. ZhouH. LiX.L. BaiF. RenQ.G. ZhangZ.J. Citalopram ameliorates synaptic plasticity deficits in different cognition-associated brain regions induced by social isolation in middle-aged rats.Mol. Neurobiol.20175431927193810.1007/s12035‑016‑9781‑x26899575
     [Google Scholar]
  37. WangL. CaoM. PuT. HuangH. MarshallC. XiaoM. Enriched physical environment attenuates spatial and social memory impairments of aged socially isolated mice.Int. J. Neuropsychopharmacol.201821121114112710.1093/ijnp/pyy08430247630
     [Google Scholar]
  38. Pereda-PérezI. ValenciaA. BaliyanS. NúñezÁ. Sanz-GarcíaA. ZamoraB. Rodríguez-FernándezR. EstebanJ.A. VeneroC. Systemic administration of a fibroblast growth factor receptor 1 agonist rescues the cognitive deficit in aged socially isolated rats.Neurobiol. Aging20197815516510.1016/j.neurobiolaging.2019.02.01130928883
     [Google Scholar]
  39. LuL. BaoG. ChenH. XiaP. FanX. ZhangJ. PeiG. MaL. Modification of hippocampal neurogenesis and neuroplasticity by social environments.Exp. Neurol.2003183260060910.1016/S0014‑4886(03)00248‑614552901
     [Google Scholar]
  40. IbiD. TakumaK. KoikeH. MizoguchiH. TsuritaniK. KuwaharaY. KameiH. NagaiT. YonedaY. NabeshimaT. YamadaK. Social isolation rearing-induced impairment of the hippocampal neurogenesis is associated with deficits in spatial memory and emotion-related behaviors in juvenile mice.J. Neurochem.2008105392193210.1111/j.1471‑4159.2007.05207.x18182044
     [Google Scholar]
  41. LieberwirthC. WangZ. The social environment and neurogenesis in the adult Mammalian brain.Front. Hum. Neurosci.2012611810.3389/fnhum.2012.0011822586385
     [Google Scholar]
  42. NiuL. LuoS.S. XuY. WangZ. LuoD. YangH. LiW. HeJ. ZhongX.L. LiuZ.H. ZengJ.Y. CaoW.Y. WanW. The critical role of the hippocampal NLRP3 inflammasome in social isolation-induced cognitive impairment in male mice.Neurobiol. Learn. Mem.202017510730110.1016/j.nlm.2020.10730132882398
     [Google Scholar]
  43. LiangT. ZhangY. WuS. ChenQ. WangL. The role of NLRP3 inflammasome in Alzheimer’s disease and potential therapeutic targets.Front. Pharmacol.20221384518510.3389/fphar.2022.84518535250595
     [Google Scholar]
  44. LiW. NiuL. LiuZ. XuX. ShiM. ZhangY. DengY. HeJ. XuY. WanW. SunQ. ZhongX. CaoW. Inhibition of the NLRP3 inflammasome with MCC950 prevents chronic social isolation-induced depression-like behavior in male mice.Neurosci. Lett.202176513629010.1016/j.neulet.2021.13629034644625
     [Google Scholar]
  45. MagalhãesD.M. MampayM. SebastiãoA.M. SheridanG.K. ValenteC.A. Age-related impact of social isolation in mice: Young vs middle-aged.Neurochem. Int.202417410567810.1016/j.neuint.2024.10567838266657
     [Google Scholar]
  46. YokoyamaM. KobayashiH. TatsumiL. TomitaT. Mouse models of Alzheimer’s disease.Front. Mol. Neurosci.20221591299510.3389/fnmol.2022.91299535799899
     [Google Scholar]
  47. HsiaoY.H. ChenP.S. ChenS.H. GeanP.W. The involvement of Cdk5 activator p35 in social isolation-triggered onset of early Alzheimer’s disease-related cognitive deficit in the transgenic mice.Neuropsychopharmacology20113691848185810.1038/npp.2011.6921544067
     [Google Scholar]
  48. HuangH.J. LiangK.C. KeH.C. ChangY.Y. Hsieh-LiH.M. Long-term social isolation exacerbates the impairment of spatial working memory in APP/PS1 transgenic mice.Brain Res.2011137115016010.1016/j.brainres.2010.11.04321114967
     [Google Scholar]
  49. HuangF. LiuX. GuoQ. MahamanY.A.R. ZhangB. WangJ.Z. LuoH. LiuR. WangX. Social isolation impairs cognition via Aβ-mediated synaptic dysfunction.Transl. Psychiatry202414138010.1038/s41398‑024‑03078‑539294141
     [Google Scholar]
  50. CaoM. HuP.P. ZhangY.L. YanY.X. ShieldsC.B. ZhangY.P. HuG. XiaoM. Enriched physical environment reverses spatial cognitive impairment of socially isolated APP swe/ PS 1dE9 transgenic mice before amyloidosis onset.CNS Neurosci. Ther.201824320221110.1111/cns.1279029274291
     [Google Scholar]
  51. HuangH. WangL. CaoM. MarshallC. GaoJ. XiaoN. HuG. XiaoM. Isolation housing exacerbates Alzheimer’s disease-like pathophysiology in aged APP/PS1 mice.Int. J. Neuropsychopharmacol.2015187pyu11610.1093/ijnp/pyu11625568286
     [Google Scholar]
  52. PetermanJ.L. WhiteJ.D. CalcagnoA. HagenC. QuiringM. PaulhusK. GurneyT. EimerbrinkM.J. CurtisM. BoehmG.W. ChumleyM.J. Prolonged isolation stress accelerates the onset of Alzheimer’s disease-related pathology in 5xFAD mice despite running wheels and environmental enrichment.Behav. Brain Res.202037911236610.1016/j.bbr.2019.11236631743728
     [Google Scholar]
  53. DongH. GoicoB. MartinM. CsernanskyC.A. BertchumeA. CsernanskyJ.G. Modulation of hippocampal cell proliferation, memory, and amyloid plaque deposition in APPsw (Tg2576) mutant mice by isolation stress.Neuroscience2004127360160910.1016/j.neuroscience.2004.05.04015283960
     [Google Scholar]
  54. DongH. YuedeC.M. YooH.S. MartinM.V. DealC. MaceA.G. CsernanskyJ.G. Corticosterone and related receptor expression are associated with increased β-amyloid plaques in isolated Tg2576 mice.Neuroscience2008155115416310.1016/j.neuroscience.2008.05.01718571864
     [Google Scholar]
  55. KangJ.E. CirritoJ.R. DongH. CsernanskyJ.G. HoltzmanD.M. Acute stress increases interstitial fluid amyloid-β via corticotropin-releasing factor and neuronal activity.Proc. Natl. Acad. Sci. USA200710425106731067810.1073/pnas.070014810417551018
     [Google Scholar]
  56. PietropaoloS. SunY. LiR. BranaC. FeldonJ. YeeB.K. Limited impact of social isolation on Alzheimer-like symptoms in a triple transgenic mouse model.Behav. Neurosci.2009123118119510.1037/a001360719170443
     [Google Scholar]
  57. MuntsantA. Giménez-LlortL. Impact of social isolation on the behavioral, functional profiles, and hippocampal atrophy asymmetry in dementia in times of Coronavirus pandemic (COVID-19): A translational neuroscience approach.Front. Psychiatry20201157258310.3389/fpsyt.2020.57258333329110
     [Google Scholar]
  58. LanooijS.D. DrinkenburgW.H.I.M. EiselU.L.M. van der ZeeE.A. KasM.J.H. The effects of social environment on AD-related pathology in hAPP-J20 mice and tau-P301L mice.Neurobiol. Dis.202318710630910.1016/j.nbd.2023.10630937748620
     [Google Scholar]
  59. RenQ.G. GongW.G. WangY.J. ZhouQ.D. ZhangZ.J. Citalopram attenuates tau hyperphosphorylation and spatial memory deficit induced by social isolation rearing in middle-aged rats.J. Mol. Neurosci.201556114515310.1007/s12031‑014‑0475‑425476250
     [Google Scholar]
  60. SayasC.L. ÁvilaJ. GSK-3 and Tau: A key duet in Alzheimer’s disease.Cells202110472110.3390/cells1004072133804962
     [Google Scholar]
  61. RissmanR.A. StaupM.A. LeeA.R. JusticeN.J. RiceK.C. ValeW. SawchenkoP.E. Corticotropin-releasing factor receptor-dependent effects of repeated stress on tau phosphorylation, solubility, and aggregation.Proc. Natl. Acad. Sci. USA2012109166277628210.1073/pnas.120314010922451915
     [Google Scholar]
  62. RoßnerS. SastreM. BourneK. LichtenthalerS.F. Transcriptional and translational regulation of BACE1 expression—Implications for Alzheimer’s disease.Prog. Neurobiol.20067929511110.1016/j.pneurobio.2006.06.00116904810
     [Google Scholar]
  63. ButterfieldD.A. Boyd-KimballD. Oxidative stress, Amyloid-β peptide, and altered key molecular pathways in the pathogenesis and progression of Alzheimer’s disease.J. Alzheimers Dis.20186231345136710.3233/JAD‑17054329562527
     [Google Scholar]
  64. GreenK.N. BillingsL.M. RoozendaalB. McGaughJ.L. LaFerlaF.M. Glucocorticoids increase amyloid-beta and tau pathology in a mouse model of Alzheimer’s disease.J. Neurosci.200626359047905610.1523/JNEUROSCI.2797‑06.200616943563
     [Google Scholar]
  65. HorganJ. Miguel-HidalgoJ.J. ThrasherM. BissetteG. Longitudinal brain corticotropin releasing factor and somatostatin in a transgenic mouse (TG2576) model of Alzheimer’s disease.J. Alzheimers Dis.200712211512710.3233/JAD‑2007‑1220117917156
     [Google Scholar]
  66. DongH. MurphyK.M. MengL. Montalvo-OrtizJ. ZengZ. KolberB.J. ZhangS. MugliaL.J. CsernanskyJ.G. Corticotrophin releasing factor accelerates neuropathology and cognitive decline in a mouse model of Alzheimer’s disease.J. Alzheimers Dis.201228357959210.3233/JAD‑2011‑11132822045495
     [Google Scholar]
  67. CampbellS.N. ZhangC. MonteL. RoeA.D. RiceK.C. TachéY. MasliahE. RissmanR.A. Increased tau phosphorylation and aggregation in the hippocampus of mice overexpressing corticotropin-releasing factor.J. Alzheimers Dis.201443396797610.3233/JAD‑14128125125464
     [Google Scholar]
  68. RiesM. SastreM. Mechanisms of Aβ clearance and degradation by glial cells.Front. Aging Neurosci.2016816010.3389/fnagi.2016.0016027458370
     [Google Scholar]
  69. TramutolaA. LanzillottaC. PerluigiM. ButterfieldD.A. Oxidative stress, protein modification and Alzheimer disease.Brain Res. Bull.2017133889610.1016/j.brainresbull.2016.06.00527316747
     [Google Scholar]
  70. HenekaM.T. KummerM.P. StutzA. DelekateA. SchwartzS. Vieira-SaeckerA. GriepA. AxtD. RemusA. TzengT.C. GelpiE. HalleA. KorteM. LatzE. GolenbockD.T. NLRP3 is activated in Alzheimer’s disease and contributes to pathology in APP/PS1 mice.Nature2013493743467467810.1038/nature1172923254930
     [Google Scholar]
  71. IsingC. VenegasC. ZhangS. ScheiblichH. SchmidtS.V. Vieira-SaeckerA. SchwartzS. AlbassetS. McManusR.M. TejeraD. GriepA. SantarelliF. BrosseronF. OpitzS. StundenJ. MertenM. KayedR. GolenbockD.T. BlumD. LatzE. BuéeL. HenekaM.T. NLRP3 inflammasome activation drives tau pathology.Nature2019575778466967310.1038/s41586‑019‑1769‑z31748742
     [Google Scholar]
  72. ZaletelI. FilipovićD. PuškašN. Hippocampal BDNF in physiological conditions and social isolation.Rev. Neurosci.201728667569210.1515/revneuro‑2016‑007228593903
     [Google Scholar]
  73. SongJ.H. YuJ.T. TanL. Brain-derived neurotrophic factor in Alzheimer’s disease: Risk, mechanisms, and therapy.Mol. Neurobiol.20155231477149310.1007/s12035‑014‑8958‑425354497
     [Google Scholar]
  74. ChoiS.H. TanziR.E. Adult neurogenesis in Alzheimer’s disease.Hippocampus202333430732110.1002/hipo.2350436748337
     [Google Scholar]
  75. HsiaoY.H. HungH.C. ChenS.H. GeanP.W. Social interaction rescues memory deficit in an animal model of Alzheimer’s disease by increasing BDNF-dependent hippocampal neurogenesis.J. Neurosci.20143449162071621910.1523/JNEUROSCI.0747‑14.201425471562
     [Google Scholar]
  76. TerraccianoA. LuchettiM. KarakoseS. StephanY. SutinA.R. Loneliness and risk of Parkinson disease.JAMA Neurol.202380111138114410.1001/jamaneurol.2023.338237782489
     [Google Scholar]
  77. GengT. LiY. PengY. ChenX. XuX. WangJ. SunL. GaoX. Social isolation and the risk of Parkinson disease in the UK biobank study.NPJ Parkinsons Dis.20241017910.1038/s41531‑024‑00700‑738589402
     [Google Scholar]
  78. DiwakarlaS. FinkelsteinD.I. ConstableR. ArtaizO. Di NataleM. McQuadeR.M. LeiE. ChaiX. RinguetM.T. FothergillL.J. LawsonV.A. EllettL.J. BergerJ.P. FurnessJ.B. Chronic isolation stress is associated with increased colonic and motor symptoms in the A53T mouse model of Parkinson’s disease.Neurogastroenterol. Motil.2020323e1375510.1111/nmo.1375531709672
     [Google Scholar]
  79. HikichiH. KondoK. TakedaT. KawachiI. Social interaction and cognitive decline: Results of a 7-year community intervention.Alzheimers Dement.201731233210.1016/j.trci.2016.11.00329067317
     [Google Scholar]
/content/journals/car/10.2174/0115672050373522250421054927
Loading
Social Isolation as a Risk Factor for Dementia: Insights from Animal Model Studies
Curr Alzheimer Res 22, 165 (2025); https://doi.org/10.2174/0115672050373522250421054927
/content/journals/car/10.2174/0115672050373522250421054927
/content/journals/car/10.2174/0115672050373522250421054927
Loading

Data & Media loading...


  • Article Type:     Review Article
Keyword(s): Alzheimer’s disease; amyloid-β; animal models; cognitive impairment; dementia; neuroinflammation; risk factor; Social isolation

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