Candidate gene association studies of the α4 (CHRNA4) and β2 (CHRNB2) neuronal nicotinic acetylcholine receptor subunit genes in Alzheimer's disease

Examination of the current top candidate genes for AD in a genome-wide association study

“…This gene, which encodes the b2-subunit of the neuronal nicotinic acetylcholine receptor, was reported to be associated with AD in a single study before 35 but the result could not be replicated in other cohorts. In this study, indirect analysis of the associated SNP also failed to unravel any significant disease association.…”

“…The strongest AD association published for the gene encoding the neuronal nicotinic acetylcholine receptor b2-subunit (CHRNB2; MIM 118507) has been with SNP rs4845378, 35 and this was also the only SNP present in the AlzGene meta-analysis of this gene. Four SNPs from the GWAS were located in CHRNB2, and an additional 12 SNPs were located less than 25 kb up-or downstream of that gene and in neighbouring genes, namely those encoding tudor domain containing 10 (TDR10), ubiquitin-conjugating enzyme E2Q (UBE2Q1) and adenosine deaminase, RNA-specific (ADAR).…”

Nicotinic Acetylcholine Receptor Signalling: Roles in Alzheimer's Disease and Amyloid Neuroprotection

“…These findings have led to the cholinergic hypothesis of AD and the development by pharmaceutical companies of therapies targeting cholinergic molecular components, so far mainly targeting the hydrolytic breakdown of ACh by AChE (Arneric et al, 2007). Genetic association studies investigating single nucleotide polymorphisms point to roles for cholinergic signaling components such as the synthetic enzyme ChAT, the inactivating enzyme AChE, and ␣4␤2 nAChRs in AD (Cook et al, 2004(Cook et al, , 2005Vasto et al, 2006). The most vulnerable neurons in AD seem to be those expressing high levels of nAChRs, particularly those containing the ␣7 subunit (D'Andrea and Nagele, 2006), and the numbers of nAChRs as well as some of their associated proteins change in AD (Martin-Ruiz et al, 1999;Gotti et al, 2006;Sabbagh et al, 2006).…”

Smoking, nicotine and neuropsychiatric disorders

“…Several studies have explored the genetic background of the relationship between the cholinergic system and AD (Vasto et al, 2007;Cook et al, 2004). Investigations into the association between a4 subunit gene polymorphisms and AD have obtained dubious results.…”