Increase of immunoglobulin G3 subclass is related to brain autoantibody in Alzheimer's disease but not in Down's syndrome

The proportions of IgG subclasses (G1, G2, G3 and G4) were quantified in sera from Alzheimer's disease (AD) patients, older Down's syndrome (DS) patients and age-matched controls. The levels of IgG1, IgG2 and IgG4 were normal in AD patients, but the proportions of IgG3 were significantly elevated in 9 of 20 (45%) patients (0.803 +/- 0.141 mg/ml; p less than 0.001) compared to the level found in age-matched controls (0.471 +/- 0.161 mg/ml; n = 10). The IgG3 level in the remaining 11 AD patients was slightly lower than the controls (0.385 +/- 0.104 vs. 0.471 +/- 0.161 mg/ml), but it did not reach statistical significance (p = 0.149). In contrast, patients with DS displayed imbalance of IgG2, IgG3, and IgG4 subclasses; they had significantly increased IgG3 but decreased IgG2 and IgG4 levels. The IgG1 level was within normal range. Moreover, a majority of AD sera (8 of 9) with elevated IgG3 concentration were positive for brain autoantibody. The remaining 11 AD sera without elevated IgG3 level, all DS sera and all control sera were negative for brain autoantibody. This finding indirectly suggests that brain autoantibody is mainly due to IgG3 subclass, at least in one subset of AD patients.