Genetic variation in the alpha 7 nicotinic acetylcholine receptor is associated with delusional symptoms in Alzheimer's disease

Neuromolecular Med. 2008;10(4):377-84. doi: 10.1007/s12017-008-8048-8. Epub 2008 Aug 12.

Abstract

Psychotic symptoms are common in Alzheimer's disease (AD) and have a negative impact on quality of life. It is suggested that psychotic symptoms may be attributed to genetic risk factors which are revealed during neurodegeneration. CHRNA7, the gene for the alpha 7 nicotinic acetylcholine receptor, has been associated with schizophrenia in linkage and association studies. Hence we investigated single SNPs and haplotypes in CHRNA7 in relation to AD with psychosis in a large, well-characterised and previously described cohort within the Northern Ireland population. A significant association between delusions and the T allele of rs6494223 (P = 0.014, OR = 1.63, CI = 1.22-2.17) was found. This suggests that the alpha 7 receptor may be a suitable target for the treatment of AD with psychosis.

MeSH terms

  • Acetylcholine / metabolism
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / complications*
  • Alzheimer Disease / genetics*
  • Alzheimer Disease / physiopathology
  • Brain Chemistry / genetics*
  • Cohort Studies
  • DNA Mutational Analysis
  • Female
  • Gene Frequency / genetics
  • Genetic Markers / genetics
  • Genetic Predisposition to Disease / genetics
  • Genetic Testing
  • Genetic Variation / genetics
  • Haplotypes
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics*
  • Receptors, Nicotinic / genetics*
  • Schizophrenia, Paranoid / genetics*
  • Schizophrenia, Paranoid / metabolism
  • Schizophrenia, Paranoid / physiopathology
  • Synaptic Transmission / genetics
  • alpha7 Nicotinic Acetylcholine Receptor

Substances

  • Chrna7 protein, human
  • Genetic Markers
  • Receptors, Nicotinic
  • alpha7 Nicotinic Acetylcholine Receptor
  • Acetylcholine