Sirtuins in Alzheimer's disease: mechanistic insights and therapeutic opportunities.

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder characterized by progressive cognitive decline and complex neuropathology. Its main features include amyloid-β (Aβ) plaques, tau neurofibrillary tangles (NFTs), and neuroinflammation. Current therapies provide only limited symptomatic relief and cannot stop disease progression, highlighting the urgent need for disease-modifying strategies. Recent research has revealed multiple roles of sirtuins in AD pathology, positioning them as promising therapeutic targets. Studies using small-molecule compounds to target sirtuins, in both cellular and animal models and clinical analyses of AD patients, demonstrate their therapeutic potential. This review discusses the distinct roles of individual sirtuin isoforms in AD pathogenesis and evaluates the therapeutic evidence for small-molecule sirtuin modulators.