Study of the GABA receptors affecting neuronal degeneration in the subjects with Alzheimer's disease

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The results of our studies are presented here. Ubiquilin 1 is shuttle protein, which modulates the expression of the GABA receptors. We examined immunohistochemically ubiquilin in the hippocampi from the controls and Alzheimer's disease (AD). In early AD cases, the intensity of ubiquilin staining appeared more robust in the pyramidal cells in CA3 and CA2 and dentate granular cells. In the majority of severely affected cases, a remarkable decrease in ubiquilin staining was observed throughout the hippocampus. These results suggest that up-regulating ubiquilin marks a compensatory response to early neurodegenerative changes. Next, We examined beta amyloid (Ab) pathology in an individual who had clinical diagnoses of probable dementia with Lewy bodies and possible AD but with no detectable [C-11]PiB PET retention ([C-11]PiB (-)) when imaged 17 months prior to death. The [C-11]PiB (-) case indicates that certain levels of Ab concentration are required to produce a positive [C-11]PiB PET signal. In the third study, we immunohistochemically examined the 5-HT1A receptor protein, which can contribute to impaired cognitive function in AD and may reduce in early AD by PET study, in the hippocampus. Our data demonstrate that hippocampal 5-HT1A receptors are mainly preserved until advanced stage of AD. It is unlikely 5-HT1A is associated with neuronal degeneration in AD brain.