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The Journal of Neuroscience, May 1, 2003, 23(9):3745
Intracranially Administered Anti-A Antibodies Reduce
-Amyloid Deposition by Mechanisms Both Independent of and Associated
with Microglial Activation
Donna M.
Wilcock1,
Giovanni
DiCarlo1,
Debbi
Henderson1,
Jennifer
Jackson1,
Keisha
Clarke1,
Kenneth E.
Ugen2,
Marcia N.
Gordon1, and
Dave
Morgan1
Departments of 1 Pharmacology and 2 Medical
Microbiology and Immunology, Alzheimer's Research Laboratory,
University of South Florida, Tampa, Florida 33612
Active immunization against the  -amyloid peptide (A) with
vaccines or passive immunization with systemic monoclonal anti-A antibodies reduces amyloid deposition and improves cognition in APP
transgenic mice. In this report, intracranial administration of
anti-A 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 was apparent at 4 hr, a dramatic reduction in the A
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 and thioflavine-S staining remained
reduced. The results from this study suggest a two-phase mechanism of
anti-A antibody action. The first phase occurs between 4 and 24 hr, clears primarily diffuse A 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.
Key words:
Alzheimer's disease; A; antibody; immunization; intracranial; phagocytosis
Copyright © 2003 Society for Neuroscience 0270-6474/03/2393745-07$05.00/0
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