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- W1985874104 abstract "The deposition of amyloid beta (Abeta) in leptomeningeal and cortical blood vessel walls induces structural changes in the vasculature of AD patients and animal models. These include localized loss of smooth muscle cells and weakening of the vessel walls, a condition known as cerebral amyloid angiopathy. Microhemorrhages are also associated with the presence of vascular Abeta deposits. We have previously shown that passive immunization with a murine form of bapineuzimab (3D6) clears vascular Abeta (VAB) in PDAPP mouse brains and subsequently re-establishes vessel wall integrity. Microhemorrhages appear with increased frequency during VAB clearance. The purpose of the present study was to determine the spatiotemporal relationship between the appearance of microhemorrhages and of changes in vessel wall structure during passive Abeta immunization. Microhemorrhage and cerebrovascular structure in leptomeningeal vessels were examined after 1, 7, 12, 24, and 36 weeks of treatment with 3D6 at 3 mg/kg. Microhemorrhage was assessed using hemosiderin detection and ferritin immunohistochemistry. The vascular integrity in the leptomeningeal vessels was assessed by quantitative immunohistochemical analysis of the vascular smooth muscle (alpha-actin) and elastic layers (collagen IV). We observed a time-dependent increase in microhemorrhages from 7 to 24 weeks of treatment and a subsequent decrease to control levels between 24 and 36 weeks. The hemosiderin staining was limited to vascular boundaries, most commonly within phagocytes. By 36 weeks of treatment, the gaps found in both the smooth muscle and collagen layers in affected vessels returned to control levels. Our data indicate that during VAB clearance by immunotherapy, microhemorrhage increases over baseline levels but is transient and resolves on a time-course that is consistent with normalization of vessel integrity." @default.
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- W1985874104 date "2011-07-01" @default.
- W1985874104 modified "2023-09-27" @default.
- W1985874104 title "P3-041: Time-course analysis of cerebral microhemorrhage and vascular structural changes during passive anti-amyloid beta immunotherapy in PDAPP mice" @default.
- W1985874104 doi "https://doi.org/10.1016/j.jalz.2011.05.1480" @default.
- W1985874104 hasPublicationYear "2011" @default.
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