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
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.