Decreased protein levels of nicotinic receptor subunits in the hippocampusand temporal cortex of patients with Alzheimer's disease

Deficits of cortical nicotinic acetylcholine receptors (nAChRs) have been o bserved in Alzheimer's disease (AD) by receptor binding assays. Little is k nown about the receptor subunit specificity influenced by AD, and it might be of importance for therapeutic strategies, In the present study, the prot ein levels of nAChR alpha 3, alpha 4, alpha 7, and beta 2 subunits were inv estigated using western blot analysis on postmortem brains of patients with AD and age-matched controls. The results showed that in human postmortem b rain samples, bands with molecular masses of 52, 42, and 50 kDa were detect ed by anti-alpha 4, anti-alpha 7, and anti-beta 2 antibodies, respectively. When anti-alpha 3 antibody was used, one major band of 49 kDa and two mino r bands of 70 and 38 kDa were detected. In AD patients, as compared with ag e-matched controls, the alpha 4 subunit was reduced significantly by simila r to 35 and 47% in the hippocampus and temporal cortex, respectively. A sig nificant reduction of 25% in the alpha 3 subunit was also observed in the h ippocampus and a 29% reduction in the temporal cortex. For the alpha 7 subu nit, the protein level was reduced significantly by 36% in the hippocampus of AD patients, but no significant change was detected in the temporal cort ex. In neither the hippocampus nor the temporal cortex was a significant di fference observed in the beta 2 subunit between AD patients and controls. T hese results reveal brain region-specific changes in the protein levels of the nAChR alpha 3, alpha 4, and alpha 7 subunits in AD.