Alterations in the Processing of Platelet APP (Amyloid Beta Precursor Protein) in Alzheimer Disease: The Possible Nexus

• Published in: Neuropsychopharmacology reports Vol. 45; no. 1; pp. e12525 - n/a
• Main Authors: Al‐kuraishy, Hayder M., Sulaiman, Ghassan M., Mohammed, Hamdoon A., Dawood, Retaj A., Albuhadily, Ali K., Al‐Gareeb, Ali I., Abomughaid, Mosleh M., Klionsky, Daniel J.
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.03.2025; John Wiley and Sons Inc; Wiley
• Subjects: activated platelets; Alzheimer Disease - blood; Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer's disease; Amyloid beta-Protein Precursor - metabolism; amyloid precursor protein; Amyloid Precursor Protein Secretases - metabolism; Animals; Blood platelets; Blood Platelets - metabolism; Cognitive ability; Cytokines; Dementia; Homeostasis; Humans; Immunity (Disease); Ligands; Metabolism; Nervous system; Neurodegeneration; Neuropathology; Oxidative stress; Pathogenesis; Peptides; Physiology; Platelet Activation - physiology; Proteins; Review; pathogenesis; activated platelets; amyloid precursor protein; Alzheimer's disease
• ISSN: 2574-173X; 2574-173X
• DOI: 10.1002/npr2.12525

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. This review examines the role of activated platelets in Alzheimer disease (AD) pathology, highlighting their contribution to amyloid peptide (Aβ) accumulation and neurofibrillary tangles. While platelets normally support neuronal health and synaptic plasticity, their overactivation may exacerbate AD. Targeting activated platelets presents a potential strategy to mitigate AD neuropathology.