RT Journal Article SR Electronic T1 Passive Amyloid Immunotherapy Clears Amyloid and Transiently Activates Microglia in a Transgenic Mouse Model of Amyloid Deposition JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 6144 OP 6151 DO 10.1523/JNEUROSCI.1090-04.2004 VO 24 IS 27 A1 Wilcock, Donna M. A1 Rojiani, Amyn A1 Rosenthal, Arnon A1 Levkowitz, Gil A1 Subbarao, Sangeetha A1 Alamed, Jennifer A1 Wilson, David A1 Wilson, Nedda A1 Freeman, Melissa J. A1 Gordon, Marcia N. A1 Morgan, Dave YR 2004 UL http://www.jneurosci.org/content/24/27/6144.abstract AB The role of microglia in the removal of amyloid deposits after systemically administered anti-Aβ antibodies remains unclear. In the current study, we injected Tg2576 APP transgenic mice weekly with an anti-Aβ antibody for 1, 2, or 3 months such that all mice were 22 months at the end of the study. In mice immunized for 3 months, we found an improvement in alternation performance in the Y maze. Histologically, we were able to detect mouse IgG bound to congophilic amyloid deposits in those mice treated with the anti-Aβ antibody but not in those treated with a control antibody. We found that Fcγ receptor expression on microglia was increased after 1 month of treatment, whereas CD45 was increased after 2 months of treatment. Associated with these microglial changes was a reduction in both diffuse and compact amyloid deposits after 2 months of treatment. Interestingly, the microglia markers were reduced to control levels after 3 months of treatment, whereas amyloid levels remained reduced. Serum Aβ levels and anti-Aβ antibody levels were elevated to similar levels at all three survival times in mice given anti-Aβ injections rather than control antibody injections. These data show that the antibody is able to enter the brain and bind to the amyloid deposits, likely opsonizing the Aβ and resulting in Fcγ receptor-mediated phagocytosis. Together with our earlier work, our data argue that all proposed mechanisms of anti-Aβ antibody-mediated amyloid removal can be simultaneously active.