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.

doi:10.1101/2025.01.24.634706

bioRxiv · 10.1101/2025.01.24.634706

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.

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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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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. Alpha-Synuclein co-pathology in Alzheimer's Disease drives tau accumulation. https://doi.org/10.1101/2025.01.24.634706

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