In the brain capillaries, endothelial cells, pericytes, astrocytes, and microglia form a structural and functional complex called neurovascular unit (NVU). In this study, we applied a comprehensive immunohistochemical approach to investigate the structural alterations in the NVU across different Alzheimer's disease (AD) neuropathological stages. Post-mortem human brain samples were immunostained using a panel of markers representing specific components of the NVU including endothelial cells, pericytes, astrocytes, microglia, and perivascular macrophages. We found an altered vascular distribution, a reduction in pericyte coverage, an increased astrocyte coverage accompanied by a decreased microglial coverage within NVU, and a relocation of perivascular macrophages from leptomeningeal arteries to penetrating parenchymal vessels in AD patients. The results of our study represent a comprehensive first in-depth analysis of AD-related structural changes of the NVU and suggest distinct alterations in all components of the NVU during AD progression.
Authors: Tunahan Kirabali, Ruslan Rust, Serena Rigotti, Alessandro Siccoli, Roger M. Nitsch, Luka Kulic.
First published: 31 August 2020