Contribution of blood platelets to vascular pathology in Alzheimer’s disease

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【标题】Contribution of blood platelets to vascular pathology in Alzheimer’s disease

【作者】 Wei Zhang  Wei Huang  Fang Jing 

【关键词】Chemokine Vessel AD Patient Platelet CAA 

【摘要】Cerebral amyloid angiopathy (CAA) is a critical factor in the pathogenesis of Alzheimer's disease (AD). In the clinical setting; nearly 98% AD patients have CAA; and 75% of these patients are rated as severe CAA. It is characterized by the deposition of the β-amyloid peptide (mainly Aβ40) in the walls of cerebral vessels; which induces the degeneration of vessel wall components; reduces cerebral blood flow; and aggravates cognitive decline. Platelets are anuclear cell fragments from bone marrow megakaryocytes and their function in hemostasis and thrombosis has long been recognized. Recently; increasing evidence suggests that platelet activation can also mediate the onset and development of CAA. First; platelet activation and adhesion to a vessel wall is the initial step of vascular injury. Activated platelets contribute to more than 90% circulating Aβ (mainly Aβ1-40); which in turn activates platelets and results in the vicious cycle of Aβ overproduction in damaged vessel. Second; the uncontrolled activation of platelets leads to a chronic inflammatory reaction by secretion of chemokines (eg; platelet factor 4 [PF4]; regulated upon activation normal T-cell expressed and presumably secreted [RANTES]; and macrophage inflammatory protein [MIP-1α]); interleukins (IL-1β; IL-7; and IL-8); prostaglandins; and CD40 ligand (CD40L). The interaction of these biological response modulators with platelets; endothelial cells; and leukocytes establishes a localized inflammatory response that contributes to CAA formation. Finally; activated platelets are the upholder of fibrin clots; which are structurally abnormal and resistant to degradation in the presence of Aβ42. Thus; opinion has emerged that targeting blood platelets may provide a new avenue for anti-AD therapy.