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

## TL;DR

This study finds that certain genetic variations in immunoglobulin genes are linked to antibody levels against amyloid-beta in Alzheimer's patients.

## Contribution

The study is the first to show that GM allotypes influence anti-amyloid-beta antibody levels in Alzheimer's disease.

## Key findings

- IgG1 GM 3/17 and IgG2 GM 23 genotypes are significantly associated with anti-Aβ antibody levels in Alzheimer's patients.
- These associations are not observed in control groups without Alzheimer's disease.
- The findings suggest GM allotypes may influence immune responses to amyloid-beta in AD.

## Abstract

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.