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

Felix L. Struebing; Xiaoxuan Song; Teodoro De Vecchi; Jeannine Widmann; Federico Fierli; Viktoria Ruf; Qilin Tang; Thomas Arzberger; Sigrun Roeber; Thomas Koeglsperger; Otto Windl; Amir Dehsarvi; Matthias Brendel; Nicolai Franzmeier; Juliane Winkelmann; Jochen Wolfgang Herms

doi:10.1101/2025.01.24.634706

NeurosciencebioRxivJan 24, 2025

Preprint

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

Felix L. Struebing iD, Xiaoxuan Song, Teodoro De Vecchi, Jeannine Widmann, Federico Fierli iD, Viktoria Ruf iD, Qilin Tang, Thomas Arzberger iD, Sigrun Roeber, Thomas Koeglsperger iD, Otto Windl iD, Amir Dehsarvi iD, Matthias Brendel, Nicolai Franzmeier iD, Juliane Winkelmann iD, Jochen Wolfgang Herms iD

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.

PDF DOI