One immune cell to bind them all: platelet contribution to neurodegenerative disease

Alzheimer's disease (AD) and related dementias (ADRD) collectively affect a significant portion of the aging population worldwide. The pathological progression of AD involves not only the classical hallmarks of amyloid beta (A beta) plaque buildup and neurofibrillary tangle development but also the effects of vasculature and chronic inflammatory processes. Recently, platelets have emerged as central players in systemic and neuroinflammation. Studies have shown that patients with altered platelet receptor expression exhibit accelerated cognitive decline independent of traditional risk factors. Additionally, platelets from AD patients exhibit heightened unstimulated activation compared to control groups. Platelet granules contain crucial AD-related proteins like tau and amyloid precursor protein (APP). Dysregulation of platelet exocytosis contributes to disease phenotypes characterized by increased bleeding, stroke, and cognitive decline risk. Recent studies have indicated that these effects are not associated with the quantity of platelets present in circulation. This underscores the hypothesis that disruptions in platelet-mediated inflammation and healing processes may play a crucial role in the development of ADRD. A thorough look at platelets, encompassing their receptors, secreted molecules, and diverse roles in inflammatory interactions with other cells in the circulatory system in AD and ADRD, holds promising prospects for disease management and intervention. This review discusses the pivotal roles of platelets in ADRD.