GABA_A receptor subunit expression changes in the human Alzheimer's disease hippocampus, subiculum, entorhinal cortex...

Gamma-aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the central nervous system. GABA type A receptors (GABA_A Rs) are severely affected in Alzheimer's disease (AD). However, the distribution and subunit composition of GABA_A Rs in the AD brain are not well understood. This is the first comprehensive study to show brain region- and cell layer-specific alterations in the expression of the GABA_A R subunits α1-3, α5, β1-3 and γ2 in the human AD hippocampus, entorhinal cortex and superior temporal gyrus. In late-stage AD tissue samples using immunohistochemistry we found significant alteration of all investigated GABA_A Rs subunits except for α3 and β1 that were well preserved. The most prominent changes include an increase in GABA_A R α1 expression associated with AD in all layers of the CA3 region, in the stratum (str.) granulare and hilus of the dentate gyrus. We found a significant increase in GABA_A R α2 expression in the str. oriens of the CA1-3, str. radiatum of the CA2,3 and decrease in the str. pyramidale of the CA1 region in AD cases. In AD there was a significant increase in GABA_A R α5 subunit expression in str. pyramidale, str. oriens of the CA1 region and decrease in the superior temporal gyrus. We also found a significant decrease in the GABA_A R β3 subunit immunoreactivity in the str. oriens of the CA2, str. granulare and str. moleculare of the dentate gyrus. In conclusion, these findings indicate that the expression of the GABA_A R subunits shows brain region- and layer-specific alterations in AD, and these changes could significantly influence and alter GABA_A R function in the disease. Cover Image for this issue: doi: 10.1111/jnc.14179.