Can platelet activation result in increased plasma Aβ levels and contribute to the pathogenesis of Alzheimer's disease?

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.