1. Association of Perivascular Localization of Aquaporin-4 With Cognition and Alzheimer Disease in Aging Brains
a. Conclusions and Relevance: In this study, altered AQP4 expression was associated with aging brains. Loss of perivascular AQP4 localization may be a factor that renders the aging brain vulnerable to the mis-aggregation of proteins, such as amyloid-β, in neurodegenerative conditions such as AD.
b. Citation: JAMA Neurology. 2017;74(1):91-99. doi:10.1001/jamaneurol.2016.4370
2. Association of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease
a. Conclusions and Relevance: The accumulation of aggregated β-amyloid and tau proteins into plaques and tangles is a central feature of Alzheimer disease (AD). While plaque and tangle accumulation likely contributes to neuron and synapse loss, disease-related changes to oligodendrocytes and myelin are also suspected of playing a role in development of AD dementia.These findings suggest amyloid pathologies significantly influence white matter and that these abnormalities may signify an early feature of the disease process. We expect that clarifying the nature of myelin damage in preclinical AD may be informative on the disease’s course and lead to new markers of efficacy for prevention and treatment trials.
Citation: JAMA Neurology. 2017;74(1):41-49. doi:10.1001/jamaneurol.2016.3232
3. R47H Variant of TREM2 Associated With Alzheimer Disease in a Large Late-Onset Family-Clinical, Genetic, and Neuropathological Study
a.Conclusion & Relevance: The R47H variant in the triggering receptor expressed on myeloid cells 2 gene (TREM2), a modulator of the immune response of microglia, is a strong genetic risk factor for Alzheimer disease (AD) and possibly other neurodegenerative disorders. Our results demonstrate a complex genetic landscape of LOAD, even in a single pedigree with an apparent autosomal dominant pattern of inheritance. Our findings support the role of the TREM2 receptor in microglial clearance of aggregation-prone proteins that is compromised in R47H carriers and may accelerate the course of disease.
b.Citation: JAMA Neurology. 2015;72(8):920-927. doi:10.1001/jamaneurol.2015.0979
4.Biomarkers for Insulin Resistance and Inflammation and the risk for Alzheimer Disease
a.Conclusions & Relevance: Our study shows that an innate pro-inflammatory cytokine response in middle age significantly contributes to AD. As these risk factors cluster in families, it is important to realize that early interventions could prevent late-onset AD. One could argue for a high-risk–prevention strategy by identifying the offspring of patients with AD, screening them for hypertension and vascular factors, and implementing various preventative health measures.
b.Citation: Arch Neurol. 2012;69(5):594-600. doi:10.1001/archneurol.2011.670
5.Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease
a.Conclusions and Relevance: Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression. We have identified genetic overlap between AD and immune-mediated diseases, implicating the HLA locus and IPMK in the pathobiology of AD. These findings provide novel insights into the relationship between inflammation and AD. Building on prior genetic and molecular evidence,31 our results are consistent with the hypothesis that rather than representing a downstream effect of neurodegeneration, inflammation influences AD pathogenesis and progression, which may have implications for treatment and prevention strategies in AD.
b.Citation: JAMA Neurol. 2016;73(6):691-697. doi:10.1001/jamaneurol.2016.0150