Background and Purpose-Cerebral microbleeds in the elderly are routinely identified by brain MRI. The purpose of this study was to better characterize the pathological basis of microbleeds. Methods-We studied postmortem brain specimens of 33 individuals with no clinical history of stroke and with an age range of 71 to 105 years. Cerebral microbleeds were identified by presence of hemosiderin (iron), identified by routine histochemistry and Prussian blue stain. Cellular localization of iron (in macrophages and pericytes) was studied by immunohistochemistry for smooth muscle actin, CD68, and, in selected cases, electron microscopy. Presence of -amyloid was analyzed using immunohistochemistry for epitope 6E10. Results-Cerebral microbleeds were present in 22 cases and occurred at capillary, small artery, and arteriolar levels.Presence of microbleeds occurred independent of amyloid deposition at site of microbleeds. Although most subjects had hypertension, microbleeds were present with and without hypertension. Putamen was the site of microbleeds in all but 1 case; 1 microbleed was in subcortical white matter of occipital lobe. Most capillary microbleeds involved macrophages, but the 2 microbleeds studied by electron microscopy demonstrated pericyte involvement. Key Words: amyloid angiopathy Ⅲ blood-brain barrier Ⅲ hemorrhage, intracerebral Ⅲ hemosiderin Ⅲ hypertension Ⅲ phagocytosis I ncreasing reliance on MRI of stroke patients has emphasized substantial prevalence and significance of cerebral microbleeds in the aging population. MRI using state-of-theart gradient-echo sequences has demonstrated cerebral microbleeds in 18% of individuals between ages 60 to 69 years and in 38% of individuals older than age 80. 1 Moreover, presence of cerebral microbleeds appears to increase risk of warfarin-associated intracerebral hemorrhage Ͼ80-fold, 2 and use of platelet aggregation inhibitors is associated with presence of microbleeds. 3 These findings underscore the importance of cerebral microbleeds.
Conclusions-TheseDespite their importance, cerebral microbleeds have received only limited attention in pathological analyses. Recent work has examined in detail cerebral microbleeds in cerebral amyloid angiopathy, 4 demonstrating strong correlation between microbleeds in postmortem brain tissue and MRI lesions. The consensus view is that microbleeds of lobar location reflect underlying cerebral amyloid angiopathy, whereas deep subcortical microbleeds indicate hypertensive vasculopathy. 1,[5][6][7][8] The purpose of the present study was to expand our knowledge of the pathology of cerebral microbleeds in the aging brain. Our focus was the vascular abnormalities underlying cerebral microbleeds, including vessel type, presence of associated amyloid angiopathy, and range of cellular involvement in the microbleeds themselves.
Materials and MethodsThe investigation consisted of 2 studies of brain tissue from elderly subjects. Initial survey study consisted of 12 subjects who underwent autopsy between January 2006 and December 2008 wit...