Interactions between Beta-Amyloid and Pericytes in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder characterized by aberrant amyloid precursor protein (APP) cleavage, pathological aggregations of beta-amyloid (Aβ) that make up Aβ plaques and hyperphosphorylation of Tau that makes up neurofibrillary tangles (NFTs). Although progress has been made in research on AD, the fundamental causes of this disease have not been fully elucidated. Recent studies have shown that vascular dysfunction especially the loss of pericytes plays a significant role in the onset of AD. Pericytes play a variety of important roles in the nervous system including the regulation of the cerebral blood flow (CBF), the formation and maintenance of the blood-brain barrier (BBB), angiogenesis, and the clearance of toxic substances from the brain. Pericytes participate in the transport of Aβ through various receptors, and Aβ acts on pericytes to cause them to constrict, detach, and die. The loss of pericytes elevates the levels of Aβ1-40 and Aβ1-42 by disrupting the integrity of the BBB and reducing the clearance of soluble Aβ from the brain interstitial fluid. The aggravated deposition of Aβ further exacerbates pericyte dysfunction, forming a vicious cycle. The combined influence of these factors eventually results in the loss of neurons and cognitive decline. Further exploration of the interactions between pericytes and Aβ is beneficial for understanding AD and could lead to the identification of new therapeutic targets for the prevention and treatment of AD. In this review, we explore the characterization of pericytes, interactions between pericytes and other cells in the neurovascular unit (NVU), and the physiological functions of pericytes and dysfunctions in AD. This review discusses the interactions between pericytes and Aβ, as well as current and further strategies for preventing or treating AD targeting pericytes.

Keywords: Alzheimer's disease; beta-amyloid; blood-brain barrier; cerebral blood flow; cognitive decline; neurovascular unit; pericytes.