RT Journal Article SR Electronic T1 Immunotherapy Reduces Vascular Amyloid-β in PDAPP Mice JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6787 OP 6793 DO 10.1523/JNEUROSCI.2377-07.2008 VO 28 IS 27 A1 Schroeter, Sally A1 Khan, Karen A1 Barbour, Robin A1 Doan, MinhTam A1 Chen, Ming A1 Guido, Terry A1 Gill, Davinder A1 Basi, Guriqbal A1 Schenk, Dale A1 Seubert, Peter A1 Games, Dora YR 2008 UL http://www.jneurosci.org/content/28/27/6787.abstract AB In addition to parenchymal amyloid-β (Aβ) plaques, Alzheimer's disease (AD) is characterized by Aβ in the cerebral vasculature [cerebral amyloid angiopathy (CAA)] in the majority of patients. Recent studies investigating vascular Aβ (VAβ) in amyloid precursor protein transgenic mice have suggested that passive immunization with anti-Aβ antibodies may clear parenchymal amyloid but increase VAβ and the incidence of microhemorrhage. However, the influences of antibody specificity and exposure levels on VAβ and microhemorrhage rates have not been well established, nor has any clear causal relationship been identified. This report examines the effects of chronic, passive immunization on VAβ and microhemorrhage in PDAPP mice by comparing antibodies with different Aβ epitopes (3D6, Aβ1–5; 266, Aβ16–23) and performing a 3D6 dose–response study. VAβ and microhemorrhage were assessed using concomitant Aβ immunohistochemistry and hemosiderin detection. 3D6 prevented or cleared VAβ in a dose-dependent manner, whereas 266 was without effect. Essentially complete absence of VAβ was observed at the highest 3D6 dose, whereas altered morphology suggestive of ongoing clearance was seen at lower doses. The incidence of microhemorrhage was increased in the high-dose 3D6 group and limited to focal, perivascular sites. These colocalized with Aβ deposits having altered morphology and apparent clearance in the lower-dose 3D6 group. Our results suggest that passive immunization can reduce VAβ levels, and modulating antibody dose can significantly mitigate the incidence of microhemorrhage while still preventing or reducing VAβ. These observations raise the possibility that Aβ immunotherapy can potentially slow or halt the course of CAA development in AD that is implicated in vascular dysfunction.