Susanne J van Veluw1, Geert Jan Biessels2, Catharina J M Klijn2, Annemieke J M Rozemuller2. 1. From the Department of Neurology, Brain Center Rudolf Magnus (S.J.v.V., G.J.B., C.J.M.K.), and the Department of Pathology (A.J.M.R.), University Medical Center Utrecht; Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Center for Neuroscience (C.J.M.K.), Radboud University Medical Center, Nijmegen; and Department of Pathology (A.J.M.R.), VU Medical Center, Amsterdam, the Netherlands. s.j.veluw-2@umcutrecht.nl. 2. From the Department of Neurology, Brain Center Rudolf Magnus (S.J.v.V., G.J.B., C.J.M.K.), and the Department of Pathology (A.J.M.R.), University Medical Center Utrecht; Department of Neurology, Donders Institute for Brain Cognition and Behaviour, Center for Neuroscience (C.J.M.K.), Radboud University Medical Center, Nijmegen; and Department of Pathology (A.J.M.R.), VU Medical Center, Amsterdam, the Netherlands.
Abstract
OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
OBJECTIVE: To investigate the histopathologic substrate of microbleeds detected on 7T postmortem MRI in autopsy cases with severe cerebral amyloid angiopathy (CAA) and Alzheimer pathology. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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