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EFFECT OF PASSIVE IMMUNOTHERAPY ON THE RATE OF PROGRESSION OF CEREBRAL AMYLOID ANGIOPATHY (CAA) IN TRANSGENIC MICE
Author(s) -
Frosch Matthew P.,
Prada Claudia M.,
Betensky Rebecca A.,
GarciaAlloza Monica,
Greenberg Steven M.,
Bacskai Brian J.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a73-d
Subject(s) - cerebral amyloid angiopathy , immunotherapy , pathology , medicine , parenchyma , amyloid (mycology) , genetically modified mouse , clearance , senile plaques , angiopathy , meningoencephalitis , alzheimer's disease , immune system , immunology , disease , transgene , chemistry , endocrinology , dementia , biochemistry , gene , diabetes mellitus , urology
Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid‐beta peptide (Aβ) in the vessel wall of arteries in the brain. Since CAA is commonly associated with Alzheimer disease (AD), characterized by parenchymal deposition of the same peptide in the form of senile plaques, there is considerable interest in the relationship of the two deposits in generating human disease. The study of CAA is of particularly important for immunotherapeutic approaches to AD, as reports of anti‐Aβ immunotherapy in mice and humans have suggested that, while CAA appeared resistant to clearance, its response to this treatment promoted potential adverse effects, including meningoencephalitis. We used multiphoton microscopy to image CAA in a mouse model of amyloid deposition to evaluate the effects of anti‐Aβ passive immunotherapy. We found detectable clearance of CAA deposits within one week following a single administration of antibody, an effect that was short‐lived. Chronic administration of antibody over 2 weeks led to more robust clearance without evidence of hemorrhage or other destructive changes. We found that the progressive clearance of Aβ from vessels follows distinct kinetics from what has been previously reported for clearance of plaques (parenchymal deposits of Aβ). This quantitative in vivo imaging approach directly demonstrates that CAA can be cleared with an optimized immunotherapy.