A pathological hallmark of Alzheimer's disease (AD) is the aggregation of amyloid-β peptides (Aβ) into fibrils, leading to deposits in cerebral parenchyma and vessels known as cerebral amyloid angiopathy (CAA). Platelets are major players of hemostasis but are also implicated in AD. Recently we provided strong evidence for a direct contribution of platelets to AD pathology. We found that monomeric Aβ40 binds through its RHDS sequence to integrin α_IIbβ₃, and promotes the formation of fibrillar Aβ aggregates by the secretion of adenosine diphosphate (ADP) and the chaperone protein clusterin (CLU) from platelets. Here we investigated the molecular mechanisms of Aβ binding to integrin α_IIbβ₃ by using Aβ11 and Aβ16 peptides. These peptides include the RHDS binding motif important for integrin binding but lack the central hydrophobic core and the C-terminal sequence of Aβ. We observed platelet adhesion to truncated N-terminal Aβ11 and Aβ16 peptides that was not mediated by integrin α_IIbβ₃. Thus, no integrin outside-in signaling and reduced CLU release was detected. Accordingly, platelet mediated Aβ fibril formation was not observed. Taken together, the RHDS motif of Aβ is not sufficient for Aβ binding to platelet integrin α_IIbβ₃ and platelet mediated Aβ fibril formation but requires other recognition or binding motifs important for platelet mediated processes in CAA. Thus, increased understanding of the molecular mechanisms of Aβ binding to platelet integrin α_IIbβ₃ is important to understand the role of platelets in amyloid pathology.

阿尔茨海默氏病（AD）的病理特征是淀粉样β肽（Aβ）聚集到原纤维中，导致在脑实质和血管中沉积，称为脑淀粉样血管病（CAA）。血小板是止血的主要参与者，但也与AD有关。最近，我们为血小板对AD病理的直接贡献提供了有力的证据。我们发现通过其RHDS序列单体Aβ40结合到整合素α _IIB β ₃，并且促进纤维状Aβ聚集体的二磷酸腺苷（ADP）和从血小板伴侣蛋白簇（CLU）的分泌的形成。在这里，我们调查了Aβ结合整合素α的分子机制_IIB β ₃通过使用Aβ11和Aβ16肽 这些肽包括对于整联蛋白结合重要的RHDS结合基序，但是缺乏中央疏水核心和Aβ的C末端序列。我们观察到血小板粘附于截短不是由整合素α介导的N-末端Aβ11和Aβ16肽_IIB β ₃。因此，未检测到整联蛋白由内而外的信号传导和减少的CLU释放。因此，未观察到血小板介导的Aβ原纤维形成。两者合计，Aβ的RHDS基序不足以Aβ结合血小板整α _IIB β ₃和血小板介导的Aβ原纤维形成，但需要其他识别或结合基序，这对CAA中的血小板介导的过程很重要。因此，增加了Aβ的分子机制的理解结合血小板整α _IIB β ₃重要的是要了解的血小板在淀粉样蛋白病理学的作用。