An immunohistochemical study of GABAA receptor gamma subunits in Alzheimer's disease hippocampus: Relationship to neurofibrillary tangle progression

Abstract

Immunohistochemical characterization of the distribution of GABA_A receptor subunits γ1/3 and 2 in the hippocampus relative to neurofibrillary tangle (NFT) pathology staging was performed in cognitively normal subjects (Braak stage I/II, n = 4) and two groups of Alzheimer's disease (AD) patients (Braak stage III/IV, n = 4; Braak stage V/VI, n = 8). In both Braak groups of AD patients, neuronal γ1/3 and γ2 immunoreactivity was preserved in all hippocampal subfields. However, compared to normal controls neuronal γ1/3 immunoreactivity was more intense in several end-stage AD subjects. Despite increased NFT pathology in the Braak V/VI AD group, GABA_Aγ1/3 and γ2 immunoreactivity did not co-localize with markers of NFT. These results suggest that upregulating or preserving GABA_Aγ1/3 and γ2 receptors may protect neurons against neurofibrillary pathology in AD.