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Impaired neuronal and synaptic function are hallmarks of early Alzheimer's disease (AD), preceding other neuropathological traits and cognitive decline. We previously showed that SFRP1, a glial-derived protein elevated in AD brains from preclinical stages, contributes to disease progression, implicating glial factors in early pathogenesis. Here, we generate and analyze transgenic mice overexpressing astrocytic SFRP1. SFRP1 accumulation causes early dendritic and synaptic defects in adult mice,...

Clonal dominance characterizes hematopoiesis during aging and increases susceptibility to blood cancers and common nonmalignant disorders. VEXAS syndrome is a recently discovered, adult-onset, autoinflammatory disease burdened by a high mortality rate and caused by dominant hematopoietic clones bearing somatic mutations in the UBA1 gene. However, pathogenic mechanisms driving clonal dominance are unknown. Moreover, the lack of disease models hampers the development of disease-modifying...

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Circular RNAs (circRNAs) are non-coding RNAs mostly derived from exons of protein-coding genes via a back-splicing process. The expression of hundreds of circRNAs accumulates during healthy aging and is associated with Alzheimer's disease (AD), which is characterized by the accumulation of amyloid-beta (Aβ) proteins. In C. elegans, many circRNAs were previously found to accumulate during aging, with loss of age-accumulated circRNAs derived from the CREB gene (circ-crh-1) to increase mean...

CONCLUSION: Olfactory decline is related to both increased cerebrovascular burden and accelerated brain atrophy over time.

CONCLUSIONS: Community-living older Americans who reside in disadvantaged counties have a higher incidence of frailty, probable dementia, and ADL disability over a 5-year follow-up period compared to their non-disadvantaged counterparts. Findings underscore the vital, underappreciated role that county-level social contextual disadvantage plays on clinically meaningful outcomes in older persons in the U.S.

“Landmark” study fingers fire-footed rope squirrel as a reservoir of fatal disease