Loss of capillary pericytes and the blood-brain barrier in white matter in poststroke and vascular dementias and Alzheimer's disease
| Autor: | 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, Elizabeta B. Mukaetova-Ladinska |
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| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | Brain Pathology |
| ISSN: | 1750-3639 |
| Popis: | 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 |
| Databáze: | OpenAIRE |
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