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

Aims: Cerebral 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. Methods: We 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. Results: PDGFR-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 %A in CADASIL compared with young controls (P<0.05). PDGFR-β %A 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. Conclusions: Our results suggest increased expression of PDGFR-β immunoreactive pericytes in cerebral microvessels in CADASIL compared with similar age controls. While we cannot confirm whether PDGFR-β-expressing pericytes produce N3ECD and hence GOM, our findings demonstrate that up-regulation of pericyte-like cells is associated with microvascular changes, including loss of vascular smooth muscle cells in CADASIL.