Department of Medicine and Surgery, Division of Psychiatry, University of Insubria, Viale Luigi Borri 57, 21100, Varese, Italy; Pisa-School of Experimental and Clinical Psychiatry, University of Pisa, Via Roma 57, 56100, Pisa, Italy.
Pisa-School of Experimental and Clinical Psychiatry, University of Pisa, Via Roma 57, 56100, Pisa, Italy.
Ageing Res Rev. 2021 Nov;71:101420. doi: 10.1016/j.arr.2021.101420. Epub 2021 Aug 8.
One of the central lesions in the brain of subjects with Alzheimer's disease (AD) is represented by aggregates of β-amyloid (Aβ), a peptide of 40-42 amino acids derived from the amyloid precursor protein (APP). The reasons why Aβ accumulates in the brain of individuals with sporadic forms of AD are unknown. Platelets are the primary source of circulating APP and, upon activation, 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. Increased platelet activity can stimulate platelet adhesion to endothelial cells, trigger the recruitment of leukocytes into the vascular wall and cause perivascular inflammation, which can spread inflammation in the brain. Neuroinflammation is fueled by activated microglial cells and reactive astrocytes that release neurotoxic cytokines and chemokines. Platelet activation is also associated with the progression of carotid artery disease resulting in an increased risk of cerebral hypoperfusion which may also contribute to the AD neurodegenerative process. Platelet activation may thus be a pathophysiological mechanism of AD and for the strong link between AD and cerebrovascular diseases. Interfering with platelet activation may represent a promising potential adjunct therapeutic approach for AD.
阿尔茨海默病（AD）患者大脑中的一个核心病变是由β-淀粉样蛋白（Aβ）聚集引起的，Aβ是一种由 40-42 个氨基酸组成的肽，源自淀粉样前体蛋白（APP）。为什么散发性 AD 患者的大脑中会积聚 Aβ，目前尚不清楚。血小板是循环 APP 的主要来源，激活后可将大量 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。血小板活性增加可刺激血小板与内皮细胞黏附，触发白细胞募集到血管壁并引起血管周围炎症，从而导致脑内炎症扩散。神经炎症是由激活的小胶质细胞和反应性星形胶质细胞引发的，这些细胞会释放神经毒性细胞因子和趋化因子。血小板激活还与颈动脉疾病的进展有关，导致大脑低灌注风险增加，这也可能导致 AD 神经退行性过程。因此，血小板激活可能是 AD 的一种病理生理机制，也是 AD 与脑血管疾病之间强关联的原因。干扰血小板激活可能是 AD 有前途的潜在辅助治疗方法。
