Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy

To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology.Five decedents (mean age at death 79.6 ± 5.7 years) with documented severe CAA and Alzheimer pathology on standard neuropathologic examination were selected from a local database. Formalin-fixed coronal brain slices were scanned at 7T MRI, including high-resolution T2- and T2*-weighted sequences. Representative microbleeds from each case were sampled for histopathologic analysis, including the presence of blood, blood breakdown products, and markers of ischemic tissue injury.On MRI, we identified >300 cortical and 4 subcortical microbleeds. Two out of 15 sampled cortical microbleeds corresponded histologically to erythrocytes (suggestive of recent hemorrhages), 4 to vasculopathies (fibrinoid necrosis in 3 and a cavernoma) without substantial parenchymal tissue injury, and 9 to accumulations of iron-positive siderophages without erythrocytes (suggestive of old hemorrhages) combined with mild to moderate degrees of chronic ischemic tissue injury.This study provides evidence for heterogeneous pathologic substrates and possibly different pathophysiologic mechanisms underlying MRI-observed cortical microbleeds in the context of advanced CAA and Alzheimer disease.