Affiliations: [a] Zilkha Neurogenetic Institute and Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA | [b] Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY, USA
Correspondence:
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Correspondence to: Berislav V. Zlokovic, MD, PhD, Zilkha Neurogenetic Institute, Keck School of Medicine, University of Southern California, 1501 San Pablo St., Los Angeles, CA 90089, USA. Tel.: +1 323 442 2566; E-mail: zlokovic@usc.edu.
Abstract: The evidence that neurovascular dysfunction is an integral part of Alzheimer's disease (AD) pathogenesis has continued to emerge in the last decade. Changes in the brain vasculature have been shown to contribute to the onset and progression of the pathological processes associated with AD, such as microvascular reductions, blood brain barrier (BBB) breakdown, and faulty clearance of amyloid β-peptide (Aβ) from the brain. Herein, we review the role of the neurovascular unit and molecular mechanisms in cerebral vascular cells behind the pathogenesis of AD. In particular, we focus on molecular pathways within cerebral vascular cells and the systemic circulation that contribute to BBB dysfunction, brain hypoperfusion, and impaired clearance of Aβ from the brain. We aim to provide a summary of recent research findings implicated in neurovascular defects and faulty Aβ vascular clearance contributing to AD pathogenesis.
Keywords: Amyloid-β clearance, blood-brain barrier, low-density lipoprotein receptor-related protein 1, pericytes, receptor for advanced glycation end products
