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Loss of capillary pericytes and the blood–brain barrier in white matter in poststroke and vascular dementias and Alzheimer’s disease

Lookup NU author(s): Dr Ren Ding, Dr Yoshiki Hase, Kamar Ameen-Ali, Michael Ndung'U, William Stevenson, Joseph Barsby, Ryan Gourlay, Tolu Akinyemi, Dr Rufus Akinyemi, Dr Tuomo Polvikoski, Dr Elizabeta Mukaetova-Ladinska, Dr Masafumi Ihara, Professor Raj Kalaria

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. White matter (WM) disease is associated with disruption of the gliovascular unit, which involves breach of the blood–brain barrier (BBB). We quantified pericytes as components of the gliovascular unit and assessed their status in vascular and other common dementias. Immunohistochemical and immunofluorescent methods were developed to assess the distribution and quantification of pericytes connected to the frontal lobe WM capillaries. Pericytes with a nucleus were identified by collagen 4 (COL4) and platelet-derived growth factor receptor-β (PDGFR-β) antibodies with further verification using PDGFR-β-specific ELISA. We evaluated a total of 124 post-mortem brains from subjects with post-stroke dementia (PSD), vascular dementia (VaD), Alzheimer’s disease (AD), AD-VaD (Mixed) and post-stroke non-demented (PSND) stroke survivors as well as normal aging controls. COL4 and PDGFR-β reactive pericytes adopted the characteristic “crescent” or nodule-like shapes around capillary walls. We estimated densities of pericyte somata to be 225 ±38 and 200 ±13 (SEM) per COL4 mm2 area or 2.0 ± 0.1 and 1.7 ± 0.1 per mm capillary length in young and older aging controls. Remarkably, WM pericytes were reduced by ~35%–45% in the frontal lobe of PSD, VaD, Mixed and AD subjects compared to PSND and controls subjects (P < 0.001). We also found pericyte numbers were correlated with PDGFR-β reactivity in the WM. Our results first demonstrate a reliable method to quantify COL4-positive pericytes and then, indicate that deep WM pericytes are decreased across different dementias including PSD, VaD, Mixed and AD. Our findings suggest that downregulation of pericytes is associated with the disruption of the BBB in the deep WM in several aging-related dementias.


Publication metadata

Author(s): Ding R, Hase Y, Ameen-Ali KE, Ndung'u M, Stevenson W, Barsby J, Gourlay R, Akinyemi T, Akinyemi R, Uemura MT, Polvikoski T, Mukaetova-Ladinska E, Ihara M, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Brain Pathology

Year: 2020

Volume: 30

Issue: 6

Pages: 1087-1101

Print publication date: 01/11/2020

Online publication date: 23/07/2020

Acceptance date: 08/07/2020

Date deposited: 15/10/2020

ISSN (print): 1015-6305

ISSN (electronic): 1750-3639

Publisher: John Wiley & Sons Ltd

URL: https://doi.org/10.1111/bpa.12888

DOI: 10.1111/bpa.12888

PubMed id: 32705757


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