Abstract TP422: Mechanisms of Cerebral Microbleeds

Abstract

Cerebral microbleeds are a common MRI finding in the aging population, and reflect an underlying microscopic pathology of cerebral microhemorrhage. Pathogenesis of cerebral microbleeds remains obscure. We conducted a mechanistic investigation of the neuropathology of cerebral microhemorrhage, combining standard and immunohistochemistry analyses, and focusing on microvascular changes concurrent with microhemorrhage. We conducted a postmortem study of participants from the UCI Alzheimer’s Disease Research Center and The 90+ Study. We analyzed five brain regions (middle frontal gyrus, occipital pole, rostral cingulate cortex, caudal cingulate cortex, and basal ganglia) of 77 brain bank subjects (aged 90±10.8 years, mean±SEM ). Prussian blue-positivity, used as an index of cerebral microhemorrhage, was subjected to quantitative analysis for all five brain regions and compared with quantitative immunohistological findings of smooth muscle actin, claudin-5, fibrinogen, and platelet-derived growth factor receptor-beta (PDGFRβ), along with the sclerosis index, a measure of arteriolar injury. The top and bottom quartiles (n=19 each) for Prussian blue-positivity were compared for immunohistological findings and for sclerosis index. Subjects from the top quartile (ie, with most extensive cerebral microhemorrhage) had significantly higher sclerosis index in all five brain regions collectively (0.355±0.008 vs 0.379±0.007; p<0.05). In addition, PDGFRβ, an index of pericyte presence, was significantly lower in the top versus bottom quartiles in caudal cingulate cortex (82±7 vs 136±15 um 2 , p<0.01). The top and bottom quartiles did not differ significantly for smooth muscle actin, fibrinogen, or claudin-5 immunoreactivity. These findings indicate significant coexistence of arteriolar injury and cerebral microhemorrhage, as well as suggesting pericyte loss concurrent with cerebral microhemorrhage. Further studies are needed to determine the presence of causal roles for arteriolar injury and pericyte loss in the pathogenesis of cerebral microbleeds.