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- W4379618061 abstract "Summary Chronic stress and elevated levels of glucocorticoids (GCs), the main stress hormones, accelerate Alzheimer’s disease (AD) onset and progression. A major driver of AD progression is the spreading of pathogenic Tau protein between brain regions, precipitated by neuronal Tau secretion. While stress and high GC levels are known to induce intraneuronal Tau pathology ( i.e. hyperphosphorylation, oligomerization) in animal models, their role in trans-neuronal Tau spreading is unexplored. Here, we find that GCs promote secretion of full-length, vesicle-free, phosphorylated Tau from murine hippocampal neurons and ex vivo brain slices. This process occurs via type 1 unconventional protein secretion (UPS) and requires neuronal activity and the kinase GSK3β. GCs also dramatically enhance trans-neuronal Tau spreading in vivo , and this effect is blocked by an inhibitor of Tau oligomerization and type 1 UPS. These findings uncover a potential mechanism by which stress/GCs stimulate Tau propagation in AD." @default.
- W4379618061 created "2023-06-08" @default.
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- W4379618061 date "2023-06-07" @default.
- W4379618061 modified "2023-10-18" @default.
- W4379618061 title "Glucocorticoid stress hormones stimulate vesicle-free Tau secretion and spreading in the brain" @default.
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- W4379618061 doi "https://doi.org/10.1101/2023.06.07.544054" @default.
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