title: Heterogeneous histopathology of cortical microbleeds in cerebral amyloid angiopathy.
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.
authors: 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.
authors: Susanne J
authors: SJ
authors: van Veluw
authors: 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.
authors: Geert Jan
authors: GJ
authors: Biessels
authors: 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.
authors: Catharina J M
authors: CJ
authors: Klijn
authors: 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.
authors: Annemieke J M
authors: AJ
authors: Rozemuller
mesh_terms: D000368:Aged; D016657:Cerebral Amyloid Angiopathy / Q000150:complications* / Q000473:pathology*; D002543:Cerebral Hemorrhage / Q000209:etiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male