Reduced vascular amyloid burden at microhemorrhage sites in cerebral amyloid angiopathy

Susanne J. van Veluw, Hugo J. Kuijf, Andreas Charidimou, Anand Viswanathan, Geert Jan Biessels, Annemieke J. M. Rozemuller, Matthew P. Frosch, Steven M. Greenberg

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 mm(2)) within a range of 315 µm surrounding the microhemorrhage, compared to control areas (2.0 per mm(2); p < 0.05). These findings question the widely held assumption that the deposition of Aβ in the walls of cortical vessels directly causes microhemorrhages.