Why does CDK5/p25 activation reduce tau phosphorylation when it's considered a major tau kinase?

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Description

The study found that higher CDK5/p25 levels were associated with lower phospho-tau amounts, directly contradicting the established dogma that CDK5 is a primary driver of tau hyperphosphorylation in AD. This fundamental contradiction challenges current therapeutic targeting strategies.

Gap type: contradiction 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)

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