We compared the intact α7 nicotinic acetylcholine receptor (α7nAChR) protein levels in the peripheral blood leukocytes in 15 Alzheimer’s disease (AD) patients and 13 normal elderly control subjects. Demographic data and Mini-Mental State Examination (MMSE) scores were obtained. Western blot analysis for α7nAChR protein levels in peripheral blood leukocytes was performed. There were no significant differences in sex and age between the AD and control groups. The mean MMSE score of the AD subjects was significantly lower than that of the normal control subjects (15.4 ± 5.5 vs. 28.5 ± 1.9 respectively; p < 0.001). The median value of normalized α7nAChR protein levels (optical density, arbitrary unit) of the AD group was significantly higher than that of the normal control group (0.6923 vs. 0.4803 respectively; p = 0.045, Mann-Whitney U test). The normalized α7nAChR protein levels showed a significant inverse correlation with the MMSE scores (Spearman rho = –0.45; p = 0.016; n = 28). Receiver Operating Characteristic curve analyses showed that the area under curve was 0.72 (95% CI 0.52– 0.87). If the cut-off of the α7nAChR protein level was >0.312, the sensitivity, specificity, positive predictive value and negative predictive value would be 80, 39, 60 and 63%, respectively. These findings showed that the α7nAChR protein levels would be a potentially useful diagnostic marker for AD.
1 Dose-ratios obtained with pirenzepine on the guinea-pig ileum at 30°C are indistinguishable from those obtained at 37°C.2 In 0.1 M NaCl at 37°C the pKa of pirenzepine for the loss of its last ionizable proton is 8.2. The ionization of pirenzepine is therefore markedly affected by changes in pH in the physiological range. 3 In experiments with pirenzepine on guinea-pig ileum and rat fundus made over a range of pH, the dose-ratio increases with the proportion of the protonated form present. As expected, the slope of the graph of dose-ratio against proportion protonated depends on the concentration of antagonist. The changes in pH produce only small effects on dose-ratios obtained with pirenzepine monomethiodide. These effects of pH can account for some of the differences between estimates of the affinity of pirenzepine. 4 The logarithm of the affinity constant of the protonated form of pirenzepine for the receptors in guinea-pig ileum is estimated to be 6.93, compared with 6.94 for the receptors in rat fundus. However, for the non-protonated form the values appear to be below 5 for the ileum compared with about 6.4 for the rat fundus.
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