Alterations in the Processing of Platelet <scp>APP</scp> (Amyloid Beta Precursor Protein) in Alzheimer Disease: The Possible Nexus
Hayder M. Al‐kuraishy, Ghassan M. Sulaiman, Hamdoon A. Mohammed, Retaj A. Dawood, Ali K. Albuhadily, Ali I. Al‐Gareeb, Mosleh Mohammad Abomughaid, Daniel J. Klionsky
Abstract
Alzheimer's disease (AD) is the most common neurodegenerative disease associated with the development of dementia. The hallmarks of AD neuropathology are accumulations of amyloid peptide (Aβ) and neurofibrillary tangles (NFTs). Aβ is derived from the processing of APP (amyloid beta precursor protein) by BACE1 (beta-secretase 1) and γ-secretase through an amyloidogenic pathway. However, processing of APP by ADAM10/α-secretase (ADAM metallopeptidase domain 10) enzymes through a non-amyloidogenic pathway produces soluble APP alpha (sAPPα), which has a neuroprotective effect. It has been shown that activated platelets are implicated in the pathogenesis of AD, which also increases platelet activation. Under physiological conditions, platelets regulate synaptic plasticity and increase neuronal differentiation by regulation of the inflammatory response. However, overactivated platelets contribute to the pathogenesis of AD. Activated platelets represent the main source of circulating APP and Aβ that may be involved in AD neuropathology. Therefore, there is a close relationship between AD neuropathology and activated platelets. This review discusses the potential role of platelets in the pathogenesis of AD, and how targeting of activated platelets may reduce AD neuropathology.