What alternative pathways drive tau hyperphosphorylation if major tau kinases are not aberrantly activated?

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Description

The findings suggest tau pathology occurs without hyperactivation of CDK5, GSK3, or ERK1/2, contradicting current models. Identifying the actual drivers of tau phosphorylation is critical for developing effective AD therapeutics targeting the right molecular mechanisms.

Gap type: open_question Source paper: Contributions of major tau kinase activation and phospho-tau accumulation to cortical and hippocampal tangle formation and cognition in older adults. (2025, Neurobiology of disease, PMID:40254098)

Evidence summary

Resolved by hypothesis h-var-08a4d5c07a: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration. Score: 0.907. Supporting PMIDs: 33875891, 30610225, 31748742, 27519954, 33741860.

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