Platelets in Alzheimer’s disease: pathogenic mechanisms and therapeutic implications

OBJECTIVES: This review examines the role of platelets, the primary peripheral source of amyloid precursor protein (APP) and amyloid-beta (Aβ), in Alzheimer's disease (AD) pathogenesis, focusing on the bidirectional feedback loop between peripheral platelet over-activation and central neuropathology, alongside potential antiplatelet therapies. METHODS: receptor modulators. RESULTS: In AD patients, platelet APP expression is markedly upregulated, shifting toward amyloidogenic processing via decreased α-secretase and increased β-secretase activity. Activated platelets breach the BBB, release pro-inflammatory mediators into the brain parenchyma, and promote cerebral Aβ deposition. Reciprocally, central AD pathology further drives systemic platelet activation, creating a self-reinforcing disease loop. CONCLUSIONS: A clear, bidirectional relationship may exist between activated platelets and AD neuropathology. Because peripheral platelets actively fuel central amyloid accumulation and neuroinflammation, targeting platelet activation may be a viable strategy to mitigate AD risk and slow disease progression.