Alzheimer’s disease (AD) is an evolving challenge that places an enormous burden on families and society. The presence of obvious brain β-amyloid (Aβ) deposition is a premise to diagnose AD, which induces the subsequent tau hyperphosphorylation and neurodegeneration. Platelets are the primary source of circulating amyloid precursor protein (APP). Upon activation, they can secrete significant amounts of Aβ into the blood, which can be actively transported to the brain across the blood-brain barrier and promote amyloid deposition. In this review, we summarized the changes in the platelet APP metabolic pathway in patients with AD and further comprehensively explored the targets and downstream events of Aβ-activated platelets. In addition, we attempted to clarify whether patients with AD are in a state of general platelet activation, with inconsistent results. Considering the increasingly evident bidirectional relationship between AD and vascular events, we speculate that the AD pathology alone seems to be insufficient to induce the general activation of platelets; however, the intervention of third-party factors, such as atherosclerosis, exposes the extracellular matrix and leads to platelet activation, further promoting AD progression. Therefore, we proposed a framework in which the relationship between platelets and AD is indirect and mediated by vascular factors. Therapies targeting platelets and interventions for vascular risk factors are likely to contribute to the prevention and treatment of AD.

阿尔茨海默病 (AD) 是一个不断发展的挑战，给家庭和社会带来了巨大的负担。存在明显的脑β-淀粉样蛋白（Aβ）沉积是诊断AD的前提，其诱导随后的tau过度磷酸化和神经变性。血小板是循环淀粉样前体蛋白 (APP) 的主要来源。激活后，它们可以将大量 Aβ 分泌到血液中，这些 Aβ 可以通过血脑屏障主动转运到大脑并促进淀粉样蛋白沉积。本综述总结了AD患者血小板APP代谢途径的变化，进一步全面探讨了Aβ活化血小板的靶点和下游事件。此外，我们试图澄清 AD 患者是否处于一般血小板活化状态，结果不一致。考虑到 AD 与血管事件之间日益明显的双向关系，我们推测仅 AD 病理学似乎不足以诱导血小板的普遍活化。然而，动脉粥样硬化等第三方因素的干预暴露了细胞外基质并导致血小板活化，进一步促进了AD的进展。因此，我们提出了一个框架，其中血小板与 AD 之间的关系是间接的并且由血管因素介导。针对血小板的疗法和针对血管危险因素的干预可能有助于预防和治疗 AD。我们推测仅 AD 病理学似乎不足以诱导血小板的一般活化；然而，动脉粥样硬化等第三方因素的干预暴露了细胞外基质并导致血小板活化，进一步促进了AD的进展。因此，我们提出了一个框架，其中血小板与 AD 之间的关系是间接的并且由血管因素介导。针对血小板的疗法和针对血管危险因素的干预可能有助于预防和治疗 AD。我们推测仅 AD 病理学似乎不足以诱导血小板的一般活化；然而，动脉粥样硬化等第三方因素的干预暴露了细胞外基质并导致血小板活化，进一步促进了AD的进展。因此，我们提出了一个框架，其中血小板与 AD 之间的关系是间接的并且由血管因素介导。针对血小板的疗法和针对血管危险因素的干预可能有助于预防和治疗 AD。我们提出了一个框架，其中血小板和 AD 之间的关系是间接的并且由血管因素介导。针对血小板的疗法和针对血管危险因素的干预可能有助于预防和治疗 AD。我们提出了一个框架，其中血小板和 AD 之间的关系是间接的并且由血管因素介导。针对血小板的疗法和针对血管危险因素的干预可能有助于预防和治疗 AD。