The big tau splice isoform resists Alzheimer's-related pathological changes
Chung, D.-e. C.; Deng, X.; Yalamanchili, H. K.; Revelli, J.-P.; Han, A. L.; Tadros, B.; Richman, R.; Dias, M.; Alavi Naini, F.; Boeynaems, S.; Hyman, B. T.; Zoghbi, H. Y.
Show abstract
In Alzheimers disease (AD), the microtubule-binding protein tau becomes abnormally hyperphosphorylated and aggregated in selective brain regions such as the cortex and hippocampus1-3. 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.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Microglia initially seed and later reshape amyloid plaques in Alzheimer's disease 97%
- Entorhinal cortex vulnerability to human APP expression promotes hyperexcitability and tau pathology 96%
- Novel brain-penetrant inhibitor of G9a methylase blocks Alzheimer’s disease proteopathology for precision medication 96%
Similar papers in this journal
Similar papers in this journal
- Tau assemblies enter the cytosol in a cholesterol sensitive process essential to seeded aggregation 97%
- Natural genetic variation determines microglia heterogeneity in wild-derived mouse models of Alzheimer's disease 94%
- A Mitochondrial Inside-Out Iron-Calcium Signal Reveals Drug Targets for Parkinsons Disease 94%
Similar papers in this journal
Similar papers in this journal
- Copper drives prion protein phase separation and modulates aggregation 94%
- Tau pathology spreads between anatomically-connected regions of the brain and is modulated by a LRRK2 mutation 94%
- Neurons burdened by DNA double strand breaks incite microglia activation through antiviral-like signaling in neurodegeneration. 93%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.