IMMUNOHISTOCHEMICAL STUDY OF GAB(A) RECEPTOR ALPHA-1 SUBUNIT IN THE HIPPOCAMPAL-FORMATION OF AGED BRAINS WITH ALZHEIMER-RELATED NEUROPATHOLOGIC CHANGES

Immunocytochemical techniques were employed to examine the distributio n of the gamma-aminobutyric acid (GABA)(A) receptor alpha 1 subunit wi thin the hippocampus of 19 elderly subjects with Alzheimer-related neu ropathologic changes. In mild cases (i.e., Braak stages I and II), the most intense neuropil immunolabeling was observed in the molecular la yer of the dentate gyrus, the stratum pyramidale of the CA1 subregion and subiculum, while the weakest labeling was observed in the CA3 subf ield. In CA4 region, the proximal dendrites and cell bodies of mossy c ells were intensely alpha 1 positive. Throughout the hippocampus, we o bserved a number of alpha 1 labeled interneurons. These cells consiste d of both large and small multipolar cells as well as small bipolar ne urons. In moderate cases (i.e., Braak stages III and IV), the pattern and intensity of alpha 1 immunolabeling appeared indistinguishable fro m mild cases. In severe cases (i.e., Braak stages V and VI), we observ ed a marked decrease in neuropil immunolabeling within the CA2, CA1 su bregions and prosubiculum, while the labeling of the molecular layer o f the dentate gyrus, subiculum proper and presubiculum was indistingui shable from mild and moderate cases. These data together with our prev ious immunocytochemical study in which we demonstrated a marked preser vation of the GABA(A) receptor subunit beta 2/3 suggest that responses of selected GABA(A) receptor subunits to AD pathology are variable wi th the alpha 1 subunit displaying a high degree of vulnerability. (C) 1998 Elsevier Science B.V. All rights reserved.