Investigating the role of tau loss‐of‐function in Alzheimer’s Disease pathogenesis

One hallmark of Alzheimer’s Disease (AD) pathology is hyperphosphorylation of tau protein, which leads to loss of its normal function and promotes aggregation into neurotoxic fibrillary tangles. While tau gain‐of‐toxic function is well‐documented, the exact role of tau loss‐of‐function in AD pathogenesis remains uncharacterized. We hypothesize that tau loss‐of‐function contributes to AD pathogenesis by activating the cellular stress response in neurons and astrocytes, characterized by cytoplasmic double‐stranded RNA (dsRNA) release, stress granule formation, and inflammation.