The Effect of Choline Acetyltransferase Genotype on Donepezil Treatment Response in Patients with Alzheimer’s Disease

Abstract

ObjectiveWe examined the difference in responses to donepezil between carriers and non-carriers of the A allele at the +4 position of the choline acetyltransferase (ChAT) gene in Koreans.MethodsPatients who met the criteria for probable Alzheimer’s disease (AD) (n=199) were recruited. Among these, 145 completed the 12-week follow-up evaluation and 135 completed the 26-week scheduled course. Differences and changes in the Korean version of the mini-mental state examination (MMSE-KC) score, Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Neuropsychological Assessment Battery (CERAD-K[N]) wordlist subtest score (WSS), CERAD-K(N) total score (TS), and the Korean version of geriatric depression scale (GDS-K) score between baseline and 12 weeks or 26 weeks were assessed by the Student’s t-test.ResultsAt 12 weeks, the changes in the MMSE-KC score, CERAD-K(N) WSS, and CERAD-K(N) TS from baseline were not significant between ChAT A allele carriers and non-carriers; however, at 26 weeks, these changes were significantly larger in ChAT A allele carriers than in non-carriers (p=0.02 for MMSE-KC and p=0.03 for CERAD-K(N) WSS respectively).ConclusionOur findings in this study suggested that presence of the A allele at the +4 position of ChAT might positively influence the treatment effect of donepezil in the early stages of AD in Koreans.

Polymorphisms of CHAT but not TFAM or VR22 are Associated with Alzheimer Disease Risk

“…Previous studies indicated that basal forebrain cholinergic neuron abnormalities are present very early in the course of AD, with altered expression of CHAT [ 47 , 48 ]. Mutations or polymorphisms of CHAT are also suspected to be related to AD and its treatment [ 49 ]. In agreement with previous results, we identified 2 SNPs of CHAT that contribute to the onset on AD.…”

Personalized genetics of the cholinergic blockade of neuroinflammation

“…; Lee et al . ). Individual variability in the cholinergic network genes may hence be pivotal for the individual variability in the efficacy of AD therapeutics.…”

“…; Lee et al . )]; Acetylcholinesterase, responsible for central degradation of ACh (Hasin et al . ; Lin et al .…”

<p>Effect of genetic polymorphisms on Alzheimer&rsquo;s disease treatment outcomes: an update</p>

“…In 2015, Lee et al12 reported that they did not observe an association between ChAT A carriers (alleles and non-carriers) and the outcomes of 12 weeks of DNP treatment. However, after 26 weeks of treatment, a considerable difference was observed in the therapeutic outcomes between A ChAT carrier alleles and non-carriers.…”