Genetic Variations in CHRNA7 or CHRFAM7 and Susceptibility to Dementia

Monica Neri, Stefano Bonassi, Patrizia Russo

Abstract

The presence of memory impairment and cognitive deficits in the Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Pick’s disease (PiD) has been associated to dysfunction of cholinergic transmission, possibly due to the loss of cholinergic neurons and to the elimination of nAChR in dementia patients. Alternative hypotheses take into account molecular interactions of the β-amyloid peptide Aβ with nAChR, which may lead to deregulation of the receptor function. Genetic polymorphisms of CHRNA7 and CHRFAM7A, a fusion gene containing a partial CHRNA7 duplication, have been investigated as possible susceptibility traits to dementia, potentially useful either to identify high risk individuals or as therapeutic targets. To summarize the existing evidence, a systematic re-evaluation of published papers has been performed (PubMed database, no language restriction, updated to 1st August 2011). Eleven articles reporting data on genetic variations in CHRNA7 or CHRFAM7 and risk of dementia fulfilled selection criteria and were evaluated. Published evidence on the association between variations in CHRNA7 or CHRFAM7A and the risk of dementia is still sparse and inconclusive. Further studies are needed to establish whether some polymorphisms may really affect the probability of developing AD or other forms of dementia. Additional and more conclusive results may come from the ongoing GWAS studies investigating high numbers of genetic variants in large samples, that have the potential to assess the role of genetic susceptibility in dementia.

Keywords: Alzheimer disease, CHRNA7, CHRFAM7A, dementia, genetic association studies, genetic polymorphism, genetic predisposition to disease, lewy bodies, Pick's disease, genome