Toggle Main Menu Toggle Search

Open Access padlockePrints

Immunolocalization of platelet-derived growth factor receptor-β (PDGFR-β) and pericytes in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL)

Lookup NU author(s): Dr Lucinda Craggs, Arthur Oakley, Dr Masafumi Ihara, Professor Raj KalariaORCiD



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


AimsCerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is identified by aggregates of NOTCH3 extracellular domain (N3ECD) along capillaries and the deposition of granular osmiophilic material (GOM). We assessed the pattern of distribution of pericytes in relation to N3ECD deposits in cerebral microvessels of CADASIL subjects.MethodsWe assessed post-mortem brains from (n=50) subjects with CADASIL, cerebral small vessel disease and similar age cognitively normal and older controls. Immunohistochemical and immunofluorescent staining methods were used to study the distribution and quantify immunoreactivities of the platelet derived growth factor receptor-β (PDGFR-β) (for pericytes) and microvascular markers in the frontal cortex and white matter.ResultsPDGFR-β antibody stained cells typical of pericytes in capillaries and small arterioles in both the grey and white matter. PDGFR-β reactive pericytes adopted “crescent” morphology wrapped closely around capillary walls readily evident in cross-sections. We noted considerable overlap between PDGFR-β and N3ECD imunoreactivities in capillaries. Quantitative analysis of PDGFR-β immunoreactivity revealed significant differences in PDGFR-β %Area in CADASIL compared to young controls (P<0.05). PDGFR-β percent Area was further positively correlated with the basement membrane marker collagen IV (r=0.529, P=0.009), but was not associated with GLUT-1, the marker for endothelial cells.ConclusionsOur results suggest increased expression of PDGFR-β immunoreactive pericytes in cerebral microvessels in CADASIL compared to similar age controls. While we cannot confirm whether PDGFR-β-expressing pericytes produce N3ECD and hence GOM, our findings demonstrate that upregulation of pericyte-like cells is associated with microvascular changes including loss of vascular smooth muscle cells in CADASIL.

Publication metadata

Author(s): Craggs LJL, Fenwick R, Oakley AE, Ihara M, Kalaria RN

Publication type: Article

Publication status: Published

Journal: Neuropathology and Applied Neurobiology

Year: 2015

Volume: 41

Issue: 4

Pages: 557-570

Print publication date: 01/06/2015

Online publication date: 23/04/2015

Acceptance date: 07/10/2014

Date deposited: 28/04/2015

ISSN (print): 0305-1846

ISSN (electronic): 1365-2990

Publisher: Wiley-Blackwell


DOI: 10.1111/nan.12188

PubMed id: 25303037


Altmetrics provided by Altmetric


Funder referenceFunder name
Alzheimer's Society
Newcastle Centre for Brain Ageing and Vitality (BBSRC)
Newcastle NIHR Biomedical Research Centre in Ageing and Age Related Diseases
Alzheimer's Research (ARUK)
ART as part of the Brains for Dementia Research Project
Newcastle Centre for Brain Ageing and Vitality (EPSRC)
Newcastle Centre for Brain Ageing and Vitality (ESRC)
Newcastle Centre for Brain Ageing and Vitality (MRC, LLHW)
G0500247UK Medical Research Council (MRC)
G0400074UK MRC
G0500247Medical Research Council (MRC)