1. Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease
- Author
-
Tolulope Akinyemi, Ren Ding, Tuomo Polvikoski, Raj N. Kalaria, Yoshiki Hase, Masafumi Ihara, Kamar E. Ameen-Ali, Ryan Gourlay, Maiko T. Uemura, Rufus Akinyemi, Joseph Barsby, William Stevenson, Michael N. Ndung’u, and Elizabeta B. Mukaetova-Ladinska
- Subjects
0301 basic medicine ,Collagen Type IV ,Male ,Pathology ,medicine.medical_specialty ,Blood–brain barrier ,pericytes ,Pathology and Forensic Medicine ,White matter ,Receptor, Platelet-Derived Growth Factor beta ,03 medical and health sciences ,0302 clinical medicine ,Alzheimer Disease ,medicine ,cerebral capillary ,Dementia ,Humans ,Vascular dementia ,platelet‐derived growth factor receptor ,Research Articles ,Aged ,Aged, 80 and over ,Neurons ,biology ,business.industry ,General Neuroscience ,Dementia, Vascular ,Brain ,vascular dementia ,Middle Aged ,medicine.disease ,White Matter ,Capillaries ,Stroke ,030104 developmental biology ,medicine.anatomical_structure ,Frontal lobe ,Blood-Brain Barrier ,biology.protein ,Immunohistochemistry ,Female ,Neurology (clinical) ,Pericyte ,business ,030217 neurology & neurosurgery ,Platelet-derived growth factor receptor ,Research Article ,dementia - Abstract
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
- Published
- 2020