Immunoglobulin γ allotypes influence the level of autoantibody responses to amyloid-β in patients with Alzheimer’s disease

Immunoglobulin GM (γ marker) allotypes, highly polymorphic hereditary antigenic determinants of IgG, have been shown to be a risk factor for the development of Alzheimer's disease (AD). The mechanisms underlying the GM-AD association are not understood. The aim of the present investigation was to determine whether GM genotypes influenced the level of naturally occurring antibodies to amyloid-β (Aβ), a hallmark of AD. We genotyped 100 AD cases and 100 controls for several GM alleles and measured antibodies to Aβ. Results showed that IgG1 GM 3/17 and IgG2 GM 23 genotypes were significantly associated with anti-Aβ antibody levels in AD cases (p = 0.014, 0.018, respectively), but not in controls (p = 0.62, 0.08, respectively). These results, for the first time, show GM allotype restriction in naturally occurring antibody responses to Aβ in individuals with AD. If confirmed, they could help devise a more potent Aβ-based immunotherapy against this neurogenerative disorder.