Department of Biology, University of Miami, Coral Gables, FL, 33146, USA.
Neuroscience Program, University of Miami Leonard M. Miller School of Medicine, Miami, FL, 33136, USA.
Mol Neurodegener. 2024 Sep 27;19(1):65. doi: 10.1186/s13024-024-00754-4.
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 (Aβ) 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.
阿尔茨海默病（AD）和相关痴呆（ADRD）共同影响着全球范围内相当一部分老龄化人口。AD 的病理进展不仅涉及淀粉样蛋白β（Aβ）斑块堆积和神经纤维缠结的经典特征，还涉及血管系统和慢性炎症过程的影响。最近，血小板已成为全身和神经炎症的核心参与者。研究表明，改变血小板受体表达的患者表现出加速认知衰退，独立于传统风险因素。此外，与对照组相比，AD 患者的血小板在未受刺激的情况下表现出更高的激活。血小板颗粒包含关键的 AD 相关蛋白，如 tau 和淀粉样前体蛋白（APP）。血小板胞吐作用的失调导致以增加出血、中风和认知衰退风险为特征的疾病表型。最近的研究表明，这些影响与循环中存在的血小板数量无关。这凸显了一个假设，即血小板介导的炎症和修复过程的紊乱可能在 ADRD 的发展中起着关键作用。全面研究血小板，包括其受体、分泌分子以及在 AD 和 ADRD 中与循环系统中其他细胞的炎症相互作用中的多种作用，为疾病管理和干预提供了有前景的思路。这篇综述讨论了血小板在 ADRD 中的关键作用。
