Intracranially Administered Anti-A beta Antibodies Reduce beta -Amyloid Deposition by Mechanisms Both Independent of and Associated with Microglial Activation

Active immunization against the beta -amyloid peptide (A beta ) with vaccines or passive immunization with systemic monoclonal anti-A beta antibodies reduces amyloid deposition and improves cognition in APP transgenic mice. In this report, intracranial administration of anti-A beta antibodies into f...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-05, Vol.23 (9), p.3745-3752
Main Authors: Wilcock, D M, DiCarlo, G, Henderson, D, Jackson, J, Clarke, K, Ugen, KE, Gordon, M N, Morgan, D
Format: Article
Language:English
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Summary:Active immunization against the beta -amyloid peptide (A beta ) with vaccines or passive immunization with systemic monoclonal anti-A beta antibodies reduces amyloid deposition and improves cognition in APP transgenic mice. In this report, intracranial administration of anti-A beta antibodies into frontal cortex and hippocampus of Tg2576 transgenic APP mice is described. The antibody injection resulted initially in a broad distribution of staining for the antibody, which diminished over 7 d. Although no loss of immunostaining for deposited A beta was apparent at 4 hr, a dramatic reduction in the A beta load was discernible at 24 hr and was maintained at 3 and 7 d. A reduction in the thioflavine-S-positive compact plaque load was delayed until 3 d, at which time microglial activation also became apparent. At 1 week after the injection, microglial activation returned to control levels, whereas A beta and thioflavine-S staining remained reduced. The results from this study suggest a two-phase mechanism of anti-A beta antibody action. The first phase occurs between 4 and 24 hr, clears primarily diffuse A beta deposits, and is not associated with observable microglial activation. The second phase occurs between 1 and 3 d, is responsible for clearance of compact amyloid deposits, and is associated with microglial activation. The results are discussed in the context of other studies identifying coincident microglial activation and amyloid removal in APP transgenic animals.
ISSN:0270-6474
DOI:10.1523/jneurosci.23-09-03745.2003