The microtubule nexus linking amyloid beta and tau: A simple and unifying theory for the underlying cause of Alzheimer's disease.

Authors

Thomas A Shoff, Maxence Derbez-Morin, Peishan Cai, Ryan R Julian

Published in

PNAS nexus. Volume 5. Issue 3. Pages pgag034. Epub Mar 17, 2026.

Abstract

Alzheimer's disease (AD) is defined by cognitive decline in conjunction with accumulation of aggregated amyloid β (Aβ) and tau, yet existing models of AD fail to provide a simple connection between Aβ and tau. However, microtubules provide an intriguing nexus for pathological interactions between the two. Tau binds to microtubules and is critical to maintaining their proper function. We demonstrate that Aβ also binds to microtubules with affinity comparable to that of tau itself. We hypothesize that displacement of tau by Aβ leads to microtubule dysfunction and facilitates tau phosphorylation and aggregation. Importantly, in this model, aggregation of Aβ is not the primary cause of toxicity, which allows many of the apparent contradictions between Aβ pathology and cognition to be rationalized. This model highlights the importance of both tau and Aβ and enables additional therapeutic and intervention strategies to be considered.

PMID:
41852647
Bibliographic data and abstract were imported from PubMed on 14 Sep 2026.

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