IMMUNOHISTOCHEMICAL STUDY OF GABA(A) RECEPTOR BETA-2 3 SUBUNITS IN THE HIPPOCAMPAL-FORMATION OF AGED BRAINS WITH ALZHEIMER-RELATED NEUROPATHOLOGIC CHANGES/

In AD, it is hypothesized that one factor contributing to the vulnerab ility of neurons is a delicate balance of excitatory and inhibitory in puts. To examine this hypothesis we have initiated a number of studies examining the role of the excitatory neurotransmitter glutamate and t he inhibitory neurotransmitter gamma-aminobutyric acid (GABA) in the n eurodegeneration of AD. As an initial investigation into the GABAergic system in AD, we employed immunocytochemical techniques and examined the distribution and density of the GABA(A) receptor subunits beta 2/3 within the hippocampus of 13 subjects with a clinical diagnosis of AD and 6 nondemented elderly subjects. Collectively, these 19 subjects p resented with a broad range of pathologic severity (i.e., Braak stages I-VI). Density measurements of nine hippocampal regions demonstrated highest levels of beta 2/3 immunolabeling in the inner molecular layer of the dentate gyrus > CA1 > CA2, while the lowest levels were found in the granular layer of the dentate gyrus less than or equal to CA4 < CA3 field. Despite these regional variations no significant differenc e in the mean density of beta 2/3 immunolabeling was observed when com paring the pathologically mild (stages I and II), moderate (stages III and rv), and severe (stages V and VI) groups. These data suggest that in the hippocampus receptor subunits associated with GABAergic neurot ransmission are relatively maintained even until the terminal stages o f the disease. (C) 1997 Academic Press.