Increased Alpha 7 Nicotinic Acetylcholine Receptor Protein Levels in Alzheimer’s Disease Patients

Abstract

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.

Intron 2 (T/C) CYP46 Polymorphism Is Associated with Alzheimer’s Disease in Chinese Patients

“…Such a discrepancy is often found in case of selection bias and regional differences in the population structure. The genotype frequency distribution of our data set fell in the range [12,13,[22][23][24] , and represented a sample size similar to those of other studies. However, the inconsistence in association analyses between the current result and those in previous reports need further clarification.…”

“…Among the published results, six studies found a positive association; however, individual observation varied about which allele conferred disease risk (two observations for T and four observations for C) [12,[22][23][24][25] . Published positive case-control studies on the genetic association of AD with the CYP46A1 intron 2 polymorphism are summarised in table 3 .…”

Anti-inflammatory role of microglial alpha7 nAChRs and its role in neuroprotection

“…The loss of the cholinergic innervation in early AD is most prominent in cortex and temporal lobes of the hippocampus [36], and it has been related to early AD cholinergic hypofunction and cognitive deficits [32]. Whether neuronal a7 nAChR are up-regulated or down-regulated in animal AD models or/and AD patients is still not fully elucidated [12,37,38]. No differences have been observed in frontal cortex and the reported loss of a7 nAChR in temporal cortex has not yet been replicated [39,40].…”

A Study on the Association of the Chromosome 12p13 Locus with Sporadic Late-Onset Alzheimer’s Disease in Chinese

“…All normal subjects had CDR ratings of CDR 0 and had no evidence of any neurological disease, while AD subjects were diagnosed in accordance to the NINCDS/ ADRDA criteria for probable AD [9] . Subjects with non-AD types of dementia, secondary causes of dementia and familial AD were excluded from the present study [10][11][12] . Family history of AD and dementia in first-degree relatives of subjects (father, mother, brother and/or sister) was reported by family members (spouse, children or sibling) of subjects during the face-to-face interviews.…”