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Alpha-Synuclein co-pathology in Alzheimer's Disease drives tau accumulation

Struebing, F. L.; De Vecchi, T.; Widmann, J.; Song, X.; Fierli, F.; Ruf, V.; Arzberger, T.; Roeber, S.; Koeglsperger, T.; Windl, O.; Haass, C.; Winkelmann, J.; Herms, J.

2025-01-27 neuroscience
10.1101/2025.01.24.634706 bioRxiv
Show abstract

The molecular basis for accelerated cognitive decline seen in Alzheimers Disease (AD) cases presenting with cortical alpha-Synuclein (-Syn) co-pathology is not well understood. We show that such co-pathology brains express higher levels of microtubule-associated protein tau and that increasing -Syn expression is sufficient to drive tau accumulation. Our results reveal a hitherto unknown link between the pathogenesis of AD and Parkinsons Disease whereby tau and -Syn synergistically drive dementia-related pathology.

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