2026/02/27 by Thomas A. Shoff, Maxence Derbez-Morin, Peishan Cai +1 · 1 voice
Biochemistry, Genetics and Molecular Biology · Medicine · #Alzheimer's disease research and treatments #Dementia and Cognitive Impairment Research #Microtubule and mitosis dynamics
paper · doi:10.1093/pnasnexus/pgag034
openalex publication_date 2026/02/27 · openalex created_date 2026/03/18 · openalex updated_date 2026/07/29
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.