Crews Lab

Univ of North Carolina Chapel Hill

PHARMACOLOGY

Chapel Hill · United States

NIH-funded
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NIH R01 · 2024

Microglia Activation and TLR-induced Neurodegeneration by Alcohol Promotes Progression of Alzheimer Pathology

Abstract Chronic heavy or binge alcohol use is associated with dementia and increased risk for Alzheimer's disease (AD), though mechanisms connecting the disease pathologies have not been identified. AD pathology follows a temporal progression of proinflammatory signaling in brain with Aβ deposition, tau fibril formation, synapse loss, neurodegeneration, and cognitive decline. We find increased AD pathology proteins Aβ1-42 and phosphorylated (p)-tau-181 in human alcohol use disorder (AUD) brain and after chronic binge ethanol during early life in the 3x- Tg-AD mouse model. Toll-like Receptor (TLR) proinflammatory signaling is thought to precede gross pathology in AD, and is a prominent…

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