Current Alzheimer Research - Volume 18, Issue 11, 2021

Background: As new biomolecular targets for Alzheimer’s disease (AD) emerge, there is a tendency to regard these as mutually exclusive and in competition, culminating in declarations that since the “amyloid hypothesis is dead” it needs to be replaced by completely different theories. However, given the well-described role of misfolding peptides, particularly β-amyloid (Aβ), in the pathogenesis of AD, the need for a broad-based conceptualization of AD, coalescing different theories into a single harmonized explanation emerges as a viable alternative. Incorporating protein aggregation mechanisms of AD into a more widely-encompassing immunopathic model of AD could accomplish such a goal-a goal which could be achieved by repositioning the role of Aβ as an immunopeptide. Conclusion: This review presents the concept that Aβ is an immunopeptide and that AD is an autoimmune disease in which Aβ is a key molecular player. Being a peptide with the capacity to alter immune function, Aβ is an immunopeptide; having both antimicrobial and immunomodulatory activities, Aβ is a host defense peptide; having most of the defining properties of cytokines, Aβ satisfies the broad definition of cytokine-the prototypic immunopeptide subtype. In addition to these immunoactivities, Aβ is also directly and independently cytotoxic to neurons by both necrotic and apoptotic mechanisms. Therefore, following brain exposure to immune-instigating stimuli, the innate immune system is activated, leading to the release of Aβ as an immunopeptide (functioning as a host defense peptide or cytokine), which subsequently inflicts a misdirected attack upon the host neurons-an autoimmune event.

The prevalence of sleep disorders and cognitive dysfunction has overwhelmingly increased, with insomnia and Alzheimer’s disease (AD) being the most common form. A multitude of studies have linked the alterations in sleep continuity or sleep architecture with cognitive impairment bilaterally, but the management of disrupted sleep patterns in preclinical AD could be more beneficial since there is no cure for AD. This review mainly focuses on the altered sleep patterns in insomnia, and summarizes potential pathways underlying the relationship between insomnia and cognitive impairment, aiming to establish certain sleep pattern changes as biomarkers for cognitive decline and explore potential therapeutic targets based on evidence from research advances.

Objective: This study assessed the ability of patients with Alzheimer’s Disease (AD) to produce “when, where, and who” information during future thinking. Methods: AD patients and control participants were invited to imagine future scenarios. Future thinking was analyzed with respect to the number of “when, where, and who” details. Analysis showed fewer “when, where, and who” details in AD participants than in control participants. Fewer “when” than “where” details and fewer “where” than “who” details were observed in AD and control participants. Results: Production of temporal information in participants with AD was found to be associated with general cognitive functioning, as assessed with the Mini Mental State Exam. Future thinking in AD is mainly associated with reduced contextual information. Conclusion: The diminished ability to construct time-related details during future thinking in AD can be mainly associated with the diminished general cognitive ability in AD, and probably with hippocampal compromise in the disease. We also propose a socio-emotional account according to which, confronted with a limited-time perspective during future thinking, AD patients may tend to maximize their emotional well-being by avoiding time-related information and thinking about friends, family and beloved ones.

Background: Alzheimer's disease (AD) is still one of the major threats to human health. Although a satisfactory treatment for AD has not yet been discovered, it is necessary to continue to search for novel approaches to deal with this insidious and debilitating disease. Although numerous studies have shown that long non-coding RNA (lncRNA) occupy a significant role in a variety of diseases, their roles in AD remain unclear. Objective: Using data analysis to explore the role of lncRNA in the course of AD, to further our understanding of AD, and to look forward to finding a new breakthrough for the treatment of AD. Methods: We downloaded and screened expression data of the hippocampal regions of patients with AD from the Gene Expression Omnibus database. We generated lncRNA-miRNA-mRNA networks based on the competing endogenous RNA (ceRNA) hypothesis, and according to gene expression level, we constructed a coding-noncoding co-expression (CNC) network and then executed cis- and trans-regulation analyses. Results: Through comprehensive and systematic analyses, we found that lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 regulated the expression of the key AD pathogenic genes APP, PSEN1, BACE1; and that these lncRNAs may promote the distribution of β-amyloid (Aβ protein) in the brain through exosomes. In addition, lncRNAs were found to adjust viral transcriptional expression, thereby further supporting viral pathogenesis for AD. Conclusion: The lncRNAs MALAT1, OIP5-AS1, LINC00657, and lnc-NUMB-1 that are present in the hippocampus of AD patients exert an important influence on the development of this disease.

Background: The Benton Visual Retention Test (BVRT) is a well-validated and reliable test for assessing visual memory and visuospatial function. However, the association between the BVRT score and imaging biomarker of Alzheimer’s disease (AD) remains unclear. Objective: This study examined whether the BVRT score is associated with brain amyloid burden and cortical glucose metabolism in elderly adults without dementia. Methods: A total of 69 elderly adults without dementia, including 45 subjects with amnestic mild cognitive impairment and 24 cognitively healthy adults, underwent the BVRT and ¹¹C-Pittsburgh compound B (PiB) and ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography. The correct scores in the BVRT were used for analyses. A multiple linear regression analysis was conducted to investigate the relationship between BVRT scores and PiB or FDG uptake. Moreover, a voxel-wise linear regression analysis of the association between BVRT scores and PiB or FDG uptake was conducted using Statistical Parametric Mapping. Results: After adjusting for age, sex, education, and ApoE4 status, the BVRT scores were inversely correlated with the mean PiB uptake (β = −0.35, P = 0.003), whereas they were positively correlated with FDG uptake (β = 0.266, P = 0.038). Moreover, the BVRT scores were inversely correlated with amyloid burden in the right superior temporal and superior frontal gyri and the left parietal lobe, whereas they were positively correlated with cortical glucose metabolism in the right posterior cingulate and milled temporal gyri, left temporoparietal lobe, and right superior frontal gyrus. Conclusion: BVRT scores are correlated with brain amyloid burden and cortical glucose metabolism, mainly in regions commonly affected in AD.