Identification of causal genes and their effects on other biological determinants untangles the complexities of aging and Alzheimer's and can facilitate drug discovery for sustaining healthy aging and treating Alzheimer's.
An internet-based cohort study of paired associate learning shows that a first-degree family history of dementia is associated with lowered performance, an effect modified by apolipoprotein E genotype and diabetes.
APPPS1 microglia express disease-associated proteomic signatures of Alzheimer's disease earlier, compared to the APP-KI, and these differences correlate with the levels of fibrillar Aβ and impaired microglial phagocytic function.
Analysis of rats carrying the microglia gene and Alzheimer risk factor Trem2R47H variant shows increased glutamatergic transmission via supraphysiological TNF-α brain concentrations, linking a microglia pathogenic variant to neuronal dysfunction.
Neuronal ELAV-like (nELAVL) proteins are associated with non-coding Y RNAs in stressed neurons and in the brains of Alzheimer's disease patients, suggesting a new means of regulatory protein sequestration and mRNA target regulation.
Translational evidence indicates APOE2 benefits longevity independent of its protective effects on Alzheimer’s disease, which preserved activity and the metabolism of apoE protein and associated-lipids would be key to understanding.