Journal Article

The Neurovascular Unit Dysfunction in Alzheimer’s Disease

Campa-Córdoba, B. Berenice, Soto-Rojas, Luis O., Apátiga-Pérez, Ricardo, Harrington, Charles R., Garcés-Ramírez, Linda, Villegas-Rojas, Marcos M., de la Cruz, Fidel, Luna-Muñoz, José, Pacheco-Herrero, Mar, Martínez-Gómez, Paola A.

2021

Overview

Alzheimer’s disease (AD) is the most common neurodegenerative disease worldwide. Histopathologically, AD presents with two hallmarks: neurofibrillary tangles (NFTs), and aggregates of amyloid β peptide (Aβ) both in the brain parenchyma as neuritic plaques, and around blood vessels as cerebral amyloid angiopathy (CAA). According to the vascular hypothesis of AD, vascular risk factors can result in dysregulation of the neurovascular unit (NVU) and hypoxia. Hypoxia may reduce Aβ clearance from the brain and increase its production, leading to both parenchymal and vascular accumulation of Aβ. An increase in Aβ amplifies neuronal dysfunction, NFT formation, and accelerates neurodegeneration, resulting in dementia. In recent decades, therapeutic approaches have attempted to decrease the levels of abnormal Aβ or tau levels in the AD brain. However, several of these approaches have either been associated with an inappropriate immune response triggering inflammation, or have failed to improve cognition. Here, we review the pathogenesis and potential therapeutic targets associated with dysfunction of the NVU in AD.

• Publisher: MDPI AG,MDPI
• Subject: Alzheimer Disease - drug therapy / Alzheimer Disease - pathology / Alzheimer Disease - physiopathology / Alzheimer's disease / Amino acids / Amyloid - metabolism / Animals / Blood-brain barrier / Blood-Brain Barrier - pathology / Blood-Brain Barrier - physiopathology / Brain / Brain - blood supply / Brain - pathology / Brain - physiopathology / Cytoskeleton / Endothelium / Humans / Lipids / Molecular Targeted Therapy / Permeability / Physiology / Proteins / Review / Veins & arteries