Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease

Title:Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease

Volume: 18 Issue: 10

Author(s): Patrizia Russo*, Aliaksei Kisialiou, Rossana Moroni, Giulia Prinzi and Massimo Fini

Affiliation:

• Laboratory of Molecular Epidemiology, IRCCS ,Italy

Keywords: Acetylcholinesterase inhibitors (AChEI), AChEI-cognitive response, AD pathogenesis, cholinergic transmission, CHRNA7, donepezil, galantamine, genetic polymorphisms (SNPs).

Abstract: Background: Cholinergic transmission loss is one of the major features in Alzheimer's Disease (AD). Acetylcholinesterase inhibitors (AChEI) are moderately active in AD. α7nAChR (alpha-7 nicotinic acetylcholine receptor), encoded by CHRNA7 (Nicotinic Cholinergic Receptor Alpha-7 gene), is involved in the cholinergic neurotransmission and AD pathogenesis. α7nAChR is a putative receptor of amyloid beta (Aβ). The complex α7nAChR-Aβ is found in neuritic plaques and AD cortical neurons. In normal physiologic conditions, α7nAChR-Aβ interaction leads to receptor activation. Genetic polymorphisms (SNPs) of CHRNA7 and/or CHRFAM7A (fusion gene containing CHRNA7 partial duplication) may be a possible susceptibility trait to dementia, potentially useful to identify high risk or responder individuals. CHRFAM7A-2-bp deletion or CHRNA7 SNPs (rs1514246, rs2337506, rs8027814) seem protective factors in different forms of dementia including AD.

Objective: Correlation between(SNPs) of CHRNA7 and/or CHRFAM7A and cholinesterase inhibitors in AD.

Methods: Literature review.

Results: Among the leading AD therapeutics, Donepezil (DP) and galantamine (AChEI) induce upregulation of α7nAChR protein levels, protecting neurons from degeneration. Patients carrying rs8024987 (C/G) or rs6494223 (C/T) respond better to AChEI. In the caucasic population rs6494223 TT subjects are 7-15% of the total. α7nAChR upregulation induced by DP is higher in lymphocytes from TT subjects than in CC or CT as well as calcium uptake.

Conclusion: The correlation between genetic and functionality data may have an impact on several aspects of disease presentation and therapy, helping in prediction pattern of AD presentation and treatment efficacy. As a consequence it may lead to better patients quality of life and longer periods of self- sufficiency. Moreover, it may contribute to clarify AChEI mechanisms of action.

Cite this article as:

Russo Patrizia*, Kisialiou Aliaksei, Moroni Rossana, Prinzi Giulia and Fini Massimo, Effect of Genetic Polymorphisms (SNPs) in CHRNA7 Gene on Response to Acetylcholinesterase Inhibitors (AChEI) in Patients with Alzheimer’s Disease, Current Drug Targets 2017; 18 (10) . https://dx.doi.org/10.2174/1389450116666151001111826

DOI https://dx.doi.org/10.2174/1389450116666151001111826	Print ISSN 1389-4501
Publisher Name Bentham Science Publisher	Online ISSN 1873-5592