Platelet-Derived Granules and Extracellular Vesicles in Neurodegenerative Diseases: Neurovascular Mechanisms and Clinical Implications.

Platelets are increasingly recognized as multifunctional regulators that extend beyond hemostasis to actively engage in immunological regulation and neurovascular homeostasis. Platelets employ specialized secretory mechanisms, including granule-dependent release and extracellular vesicle (EV) shedding, to convey diverse bioactive mediators to vascular, immune, and neural cells. Growing evidence indicates that platelet-derived granules and EVs significantly influence the neurovascular unit, regulate inflammatory signaling, and modify neuronal function in both health and disease. In neurodegenerative disorders, particularly Alzheimer's disease (AD), accumulating evidence suggests that platelet activation may be increased in neurodegenerative conditions, including AD, although the extent and causality of this activation remain under investigation. This review delineates the secretory apparatus of platelets and their mechanistic functions in intercellular communication, underscores platelet contributions to AD and other neurological disorders, and explores novel clinical prospects for biomarker development and therapeutic targeting based on platelet-derived EVs.