Language
English
Publication Date
7-31-2024
Journal
bioRxiv
DOI
10.1101/2024.07.30.605685
PMID
39211086
PMCID
PMC11360890
PubMedCentral® Posted Date
7-31-2024
PubMedCentral® Full Text Version
Pre-Print
Abstract
In Alzheimer’s disease (AD), the microtubule-binding protein tau becomes abnormally hyperphosphorylated and aggregated in selective brain regions such as the cortex and hippocampus 1–3 . However, other brain regions like the cerebellum and brain stem remain largely intact despite the universal expression of tau throughout the brain. Here, we found that an understudied splice isoform of tau termed “big tau” is significantly more abundant in the brain regions less vulnerable to tau pathology compared to tau pathology-vulnerable regions. We used various cellular and animal models to demonstrate that big tau possesses multiple properties that can resist AD-related pathological changes. Importantly, human AD patients show a higher expression level of pathology-resisting big tau in the cerebellum, the brain region spared from tau pathology. Our study examines the unique properties of big tau, expanding our current understanding of tau pathophysiology. Altogether, our data suggest that alternative splicing to favor big tau is a viable strategy to modulate tau pathology.
Published Open-Access
yes
Recommended Citation
Revelli, Jean-Pierre; Han, Alexander L; Tadros, Bakhos; et al., "The Big Tau Splice Isoform Resists Alzheimer’s-Related Pathological Changes" (2024). Faculty, Staff and Students Publications. 8382.
https://digitalcommons.library.tmc.edu/baylor_docs/8382