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

Abstract

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.

Changes in Regional Cerebral Blood Flow Are Associated With Endothelial Dysfunction Markers in Cocaine-Dependent Patients Under Recent Abstinence

“…The activation of platelets leads to a chronic inflammatory reaction through the secretion of chemokines such as RANTES, which may contribute to cerebral vascular derangement and blood flow perturbations (Zhang et al, 2013). Our observations of the association between RANTES levels and rCBF seem to suggest the same relationship.…”

Integrative Systems Biology Investigation of Fabry Disease

“…Platelet granule secretion has an important role in the pathogenesis of ischemic cardio- and cerebrovascular diseases [40,41]. Additionally, the release of prostaglandin (PTGDS catalyses the conversion of PGH2 to PGD2) mediators of the inflammation process can contribute to its resolution and promote wound healing (ANXA1, and ANXA2).…”

Pathogen inactivation of double‐dose buffy‐coat platelet concentrates photochemically treated with amotosalen and UVA light: preservation of in vitro function

“…A large variety of factors is released from PLTs [49,50] and is found present in PLT concentrates [25,33,[51][52][53][54]. Because of the potentially harmful effects [35, [55][56][57][58] of PLT derived factors, it is of major importance that a PI technology does not exacerbate such negative events. The data presented in this study demonstrate accumulation of sCD40L in all PLT units during storage.…”