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Previous Article | Next Article
The Journal of Neuroscience, September 15, 2002, 22(18):7873-7878
Non-Fc-Mediated Mechanisms Are Involved in Clearance of Amyloid-
In Vivo by Immunotherapy
Brian J. Bacskai1, Stephen T. Kajdasz1, Megan E. McLellan1, Dora Games2, Peter Seubert2, Dale Schenk2, and Bradley T. Hyman1 1 Alzheimer's Disease Research Laboratory, Massachusetts General Hospital, Charlestown, Massachusetts 02129, and 2 Elan Pharmaceuticals, South San Francisco, California 94080
Transgenic (Tg) mouse models overexpressing amyloid precursor protein (APP) develop senile plaques similar to those found in Alzheimer's disease in an age-dependent manner. Recent reports demonstrated that immunotherapy is effective at preventing or removing amyloid-
deposits in the mouse models. To characterize the mechanisms involved in clearance, we used antibodies of either IgG1 (10d5) or IgG2b (3d6) applied directly to the brains of 18-month-old Tg2576 or 20-month-old PDAPP mice. Both 10d5 and 3d6 led to clearance of 50% of diffuse amyloid deposits in both animal models within 3 d. Fc receptor-mediated clearance has been shown to be important in an ex vivo assay showing antibody-mediated clearance of plaques by microglia. We now show, using in vivo multiphoton microscopy, that FITC-labeled F(ab')2 fragments of 3d6 (which lack the Fc region of the antibody) also led to clearance of 45% of the deposits within 3 d, similar to the results obtained with full-length 3d6 antibody. This result suggests that direct disruption of plaques, in addition to Fc-dependent phagocytosis, is involved in the antibody-mediated clearance of amyloid-
Key words: amyloid; transgenic; Alzheimer; multiphoton; imaging; senile plaque; microglia; immunotherapy; antibody
Copyright © 2002 Society for Neuroscience 0270-6474/02/22187873-06$05.00/0
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