IVIG products contain antibodies to Aβ oligomers and fibrils
[
34] and perhaps also to monomeric Aβ
[
11,
35]. These drugs differ in their levels of anti-Aβ antibodies
[
10‐
12]. IVIG has been shown
in vitro to disaggregate preformed Aβ fibrils, promote Aβ phagocytic removal
[
36], protect against Aβ neurotoxicity
[
35,
37], and prevent formation of Aβ soluble oligomers
[
11]. But studies in mouse models of AD have produced conflicting results as to whether IVIG products can reduce brain Aβ. Magga et al.
[
38] found that Gammagard promoted microglial-mediated clearance of Aβ in experiments with brain sections from APP/PS1 mice and reduced
in vitro Aβ fibril formation, but the latter effect was not specific for its anti-Aβ antibodies. Dodel et al.
[
37] treated APP695 double mutant mice with purified anti-Aβ antibodies from Octagam for 4 weeks beginning at 3 or 12 months of age. Reduced plaque counts were found in the younger mice but not in the older mice. Puli et al.
[
39] treated TgApdE9 mice with Gammagard beginning at 4 months of age, for 3 or 8 months. In the 3-month-treated group, there were no effects on hippocampal plaque counts or brain Aβ. After 8 months, there were still no differences in plaque counts between treatment and control groups. Surprisingly, soluble Aβ levels in hippocampus were increased in treated mice.
IVIG’s antibodies recognize multiple sites on conformational Aβ epitopes, and its main binding to Aβ is reportedly to Aβ25-40
[
12,
37]. This differs from the monoclonal anti-Aβ antibodies that have been used in clinical trials, Bapineuzumab and Solanezumab, which recognize only one epitope in linear Aβ and bind to Aβ1-5 and Aβ13-28, respectively
[
40]. A recent review
[
41] suggested that using the IVIG polyclonal antibody approach in an effort to deplete the spectrum of aggregated Aβ species might be more promising than using monoclonal antibodies targeting a single Aβ species.