title: Reduced vascular amyloid burden at microhemorrhage sites in cerebral amyloid angiopathy.
abstract: Microhemorrhages are strongly associated with advanced cerebral amyloid angiopathy (CAA). Although it has been frequently proposed that the deposition of Aβ in the walls of cortical vessels directly causes microhemorrhages, this has not been studied in great detail, mainly because the ruptured vessels are often missed on routine histopathologic examination. Here, we examined histopathological data from studies targeting microhemorrhages with high-resolution ex vivo 7 T MRI in nine cases with moderate-to-severe CAA, and assessed the presence of Aβ in the walls of involved vessels. We also assessed the density of Aβ positive cortical vessels in areas surrounding microhemorrhages compared to control areas. In seven out of 19 microhemorrhages, the presumed involved vessel could be identified on the histopathological section. Only one of these vessels was positive for Aβ at the site of rupture. Moreover, the density of Aβ positive cortical vessels was lower (1.0 per mm2) within a range of 315 µm surrounding the microhemorrhage, compared to control areas (2.0 per mm2; p < 0.05). These findings question the widely held assumption that the deposition of Aβ in the walls of cortical vessels directly causes microhemorrhages.
authors: Department of Neurology, J. Philip Kistler Stroke Research Center, Harvard Medical School, Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA. svanveluw@mgh.harvard.edu.|Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands. svanveluw@mgh.harvard.edu.
authors: Susanne J
authors: SJ
authors: van Veluw
authors: Image Sciences Institute, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Hugo J
authors: HJ
authors: Kuijf
authors: Department of Neurology, J. Philip Kistler Stroke Research Center, Harvard Medical School, Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA.
authors: Andreas
authors: A
authors: Charidimou
authors: Department of Neurology, J. Philip Kistler Stroke Research Center, Harvard Medical School, Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA.
authors: Anand
authors: A
authors: Viswanathan
authors: Department of Neurology, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, The Netherlands.
authors: Geert Jan
authors: GJ
authors: Biessels
authors: Department of Pathology, VU Medical Center, Amsterdam, The Netherlands.
authors: Annemieke J M
authors: AJ
authors: Rozemuller
authors: Neuropathology Service, C.S. Kubik Laboratory for Neuropathology, Harvard Medical School, Massachusetts General Hospital, Boston, MA, USA.
authors: Matthew P
authors: MP
authors: Frosch
authors: Department of Neurology, J. Philip Kistler Stroke Research Center, Harvard Medical School, Massachusetts General Hospital, 175 Cambridge Street, Suite 300, Boston, MA, 02114, USA.
authors: Steven M
authors: SM
authors: Greenberg
mesh_terms: D058227:Amyloidogenic Proteins / Q000378:metabolism*; D016657:Cerebral Amyloid Angiopathy / Q000150:complications*; D002540:Cerebral Cortex / Q000473:pathology; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D020300:Intracranial Hemorrhages / Q000000981:diagnostic imaging / Q000209:etiology* / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male
chemical_list: D058227:Amyloidogenic Proteins
keywords: Amyloid β; MRI; Microbleeds; Small vessel disease