This paper describes a mechanism by which macrophages may participate in the development of congophilic amyloid angiopathy. The results are consistent with Aβ-engorged macrophages being unable to transit across the endothelial cell barrier, ultimately succumbing to toxic actions of extracellular Aβ, and disgorging their contents near the vessels. Such a mechanism may explain why anti-Aβ antibodies promote congophilic angiopathy, which by itself may increase the risk of microhemorrhage, as observed with immunotherapy (Pfeifer et al., 2003; Wilcock et al., 2004; Racke et al., 2005; Schroeder et al., 2008; Boche et al., 2008). The mechanisms may also explain why antibodies which do not facilitate macrophage phagocytosis, via Fc receptor interactions, may minimize these potentially adverse consequences (Wilcock et al., 2006).
Wilcock DM, Alamed J, Gottschall PE, Grimm J, Rosenthal A, Pons J, Ronan V, Symmonds K, Gordon MN, Morgan D. Deglycosylated anti-amyloid-beta antibodies eliminate cognitive deficits and reduce parenchymal amyloid with minimal vascular consequences in aged amyloid precursor protein transgenic mice. J Neurosci. 2006 May 17;26(20):5340-6. Abstract
Wilcock DM, Rojiani A, Rosenthal A, Subbarao S, Freeman MJ, Gordon MN, Morgan D. Passive immunotherapy against Abeta in aged APP-transgenic mice reverses cognitive deficits and depletes parenchymal amyloid deposits in spite of increased vascular amyloid and microhemorrhage. J Neuroinflammation. 2004 Dec 8;1(1):24. Abstract
Pfeifer M, Boncristiano S, Bondolfi L, Stalder A, Deller T, Staufenbiel M, Mathews PM, Jucker M. Cerebral hemorrhage after passive anti-Abeta immunotherapy. Science. 2002 Nov 15;298(5597):1379. Abstract
Racke MM, Boone LI, Hepburn DL, Parsadainian M, Bryan MT, Ness DK, Piroozi KS, Jordan WH, Brown DD, Hoffman WP, Holtzman DM, Bales KR, Gitter BD, May PC, Paul SM, Demattos RB. Exacerbation of cerebral amyloid angiopathy-associated microhemorrhage in amyloid precursor protein transgenic mice by immunotherapy is dependent on antibody recognition of deposited forms of amyloid beta. J Neurosci. 2005 Jan 19;25(3):629-36. Abstract
Schroeter S, Khan K, Barbour R, Doan M, Chen M, Guido T, Gill D, Basi G, Schenk D, Seubert P, Games D. Immunotherapy reduces vascular amyloid-beta in PDAPP mice. J Neurosci. 2008 Jul 2;28(27):6787-93. Abstract
Boche D, Zotova E, Weller RO, Love S, Neal JW, Pickering RM, Wilkinson D, Holmes C, Nicoll JA. Consequence of Abeta immunization on the vasculature of human Alzheimer's disease brain. Brain. 2008 Dec;131(Pt 12):3299-310. Abstract
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