Immunohistochemical study of GABAA receptor α1 subunit in the hippocampal formation of aged brains with Alzheimer-related neuropathologic changes

Immunocytochemical techniques were employed to examine the distribution of the γ-aminobutyric acid (GABA)_A receptor α1 subunit within the hippocampus of 19 elderly subjects with Alzheimer-related neuropathologic changes. In mild cases (i.e., Braak stages I and II), the most intense neuropil immunolabeling was observed in the molecular layer of the dentate gyrus, the stratum pyramidale of the CA1 subregion and subiculum, while the weakest labeling was observed in the CA3 subfield. In CA4 region, the proximal dendrites and cell bodies of mossy cells were intensely α1 positive. Throughout the hippocampus, we observed a number of α1 labeled interneurons. These cells consisted of both large and small multipolar cells as well as small bipolar neurons. In moderate cases (i.e., Braak stages III and IV), the pattern and intensity of α1 immunolabeling appeared indistinguishable from mild cases. In severe cases (i.e., Braak stages V and VI), we observed a marked decrease in neuropil immunolabeling within the CA2, CA1 subregions and prosubiculum, while the labeling of the molecular layer of the dentate gyrus, subiculum proper and presubiculum was indistinguishable from mild and moderate cases. These data together with our previous immunocytochemical study in which we demonstrated a marked preservation of the GABA_A receptor subunit β2/3 suggest that responses of selected GABA_A receptor subunits to AD pathology are variable with the α1 subunit displaying a high degree of vulnerability.