Targeting STAT3 in Alzheimer's disease: Potential mechanisms and therapeutic implications

Alzheimer's disease (AD) is the leading cause of dementia worldwide, with no disease-modifying treatments to halt or reverse progressive neurodegeneration. Chronic neuroinflammation is a core unresolved pathological driver of AD, and signal transducer and activator of transcription 3 (STAT3) has emerged as a critical yet controversial master mediator of the associated neuroinflammatory and neurodegenerative processes. This review systematically explores the multifaceted, cell-type-specific relationship between STAT3 signaling and AD pathology, focusing on its roles in neuroinflammation, amyloid precursor protein processing, tau phosphorylation, neuronal survival, and synaptic function. We further critically evaluate therapeutic strategies targeting STAT3 pathways in AD, underscoring the immediate relevance of STAT3 as both a promising biomarker and a tractable target for translational drug development.