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Deficits of cortical nicotinic acetylcholine receptors (nAChRs) have been observed in Alzheimer's disease (AD) by receptor binding assays. Little is known about the receptor subunit specificity influenced by AD, and it might be of importance for therapeutic strategies. In the present study, the protein levels of nAChR ␣3, ␣4, ␣7, and ␤2 subunits were investigated using western blot analysis on postmortem brains of patients with AD and age-matched controls. The results showed that in human postmortem brain samples, bands with molecular masses of 52, 42, and 50 kDa were detected by anti-␣4, anti-␣7, and anti-␤2 antibodies, respectively. When anti-␣3 antibody was used, one major band of 49 kDa and two minor bands of 70 and 38 kDa were detected. In AD patients, as compared with age-matched controls, the ␣4 subunit was reduced significantly by ϳ35 and 47% in the hippocampus and temporal cortex, respectively. A significant reduction of 25% in the ␣3 subunit was also observed in the hippocampus and a 29% reduction in the temporal cortex. For the ␣7 subunit, the protein level was reduced significantly by 36% in the hippocampus of AD patients, but no significant change was detected in the temporal cortex. In neither the hippocampus nor the temporal cortex was a significant difference observed in the ␤2 subunit between AD patients and controls. These results reveal brain region-specific changes in the protein levels of the nAChR ␣3, ␣4, and ␣7 subunits in AD. Key Words: Alzheimer's disease-Neuronal nicotinic acetylcholine receptor-Postmortem brain-Western blot.

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The alpha7 subunit of nicotinic receptor (nAChR) was investigated in post-mortem brain tissue from eight schizophrenics and eight age-matched controls by Western blot. Using anti-alpha7 antibodies a single band with a mol. wt of 42 kDa was detected in human post-mortem brain, which was smaller in size than the single band (52 kDa) detected in SH-SY5Y and PC12 cells. The smaller band specifically bound to [125I]alpha-bungarotoxin, confirming the specificity of the detection in the human brain samples. A significant decrease in the level of alpha7 subunit protein was observed with the same method in the frontal cortex of schizophrenics compared with controls, while no difference was found in the parietal cortex. These findings suggest that a deficit of nAChR alpha7 subunit in the frontal cortex might be involved in the pathophysiology of schizophrenia.

Rivastigmine causes persistent inhibition of AChE and BuChE in CSF as well as plasma. The persistent CSF inhibition contrasts with earlier findings after long-term treatment by the reversible ChE inhibitor tacrine, which demonstrated increased AChE activity in the CSF but not in the blood. Rivastigmine's effects on the preferential up-regulation of the AChE-R isoform may have a favorable effect on disease stabilization.

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Several lipid modifications, some of which were attributed to oxidative stress, have been reported in the brains of patients with Alzheimer disease (AD). To evaluate this possibility, all phospholipids and their ether subclasses from the frontal cortex, hippocampus, and the white matter of AD brain were analyzed by high performance liquid chromatography and gas chromatography. The total phospholipid in the frontal cortex and hippocampus decreased on a DNA basis by about 20% and this change was essentially explained by a selective decrease in phosphatidylethanolamine and phosphatidylcholine. The lower content of phosphatidylethanolamine was due to a specific decrease in the plasmalogen subclass. Phosphatidylethanolamine plasmalogen was also the only lipid exhibiting major structural modifications: a significant decrease in polyunsaturated fatty acids and oleic acid as well as a shift of the aldehyde pattern from 18:1 to 18:0. The only modification observed in the other phospholipids was a decrease in oleic acid in diacyl-phosphatidylethanolamine and diacyl-phosphatidylcholine. None of these changes were observed in the white matter. Both the vinyl ether bond of phosphatidylethanolamine plasmalogen and polyunsaturated fatty acids are major targets in oxidative stress; thus, these specific lipid modifications strongly support the involvement of free radicals in the pathogenesis of AD.

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