(P25-012-25) Phosphatidylethanolamine N-methyltransferase G175A Modifies Methyl Donor Intake Requirements and Alzheimer’s-Related Biomarkers for Predicting Cognitive Dysfunction

Objectives: The phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway involving in the conversion of PE to phosphotidylcholine (PC) via 3 folate- and betaine-mediated methylation reactions to account for 30% PE synthesis, the important component for neural health and cognition function. We hypothesize the genetic polymorphism of PEMT rs12325817 at G175A loci as the Alzheimer's disease (AD) risk SNP to modify methyl donors requirement and AD-associated risk factors for normal cognition function.

Methods: To test the hypothesis, we conduct the TMDNADP study(Taiwanese Methyl Donors Nutrition and AD prevention) to recruit elderly subjects from the department of Neurology in the National Taiwan University Hospital and Fu Jen Catholic University Hospital. 

Results: The results showed that PEMT GA/AA genotype vs. GG wild type was associated with higher BMI, elevated blood pTau levels, and cognition dysfunction evaluated by CDR as well as MMSE . Habitual folate intake below elderly RDA(400 ug/day) was 41% in GG carriers and 40% in GA/AA carriers. Habitual total choline intake below elderly AI (men: 450 mg/day; women: 400 mg/day) was 68% in GG carriers and 40% in GA/AA carriers. Habitual Intake of phosphotidylcholine and betaine significantly differ in elderly with GG vs. GA/AA genotype, with no statistical significance in habitual macronutrients intake and energy consumption. For those with GA/AA genotype, adequate choline intake ( > elderly AI) vs. insufficient intake (< elderly AI) was associated with higher MMSE score and lower blood homocysteine, with significant gene and choline intake interaction in Hcy levels. Similar effect of adequate folate intake on higher MMSE score was observed in GA/AA carriers. For those with insufficient choline intake, the GA/AA carriers had significantly higher blood pTau levels and Hcy levels than the GA/AA carriers. After adjustment for age, sex, BMI and education level, increased energy adjusted-choline intake was significantly associated with increased MMSE score in GA/AA carriers.

Conclusions: Taken together, the data unveil the genetic polymorphism of PEMT rs12325817 at G175A loci as the AD risk SNP to interact with habitual choline intake and modify early and late AD markers of blood pTau levels as well as cognition dysfunction.

Funding Sources: NSTC 113-2321-B-030-001; NSTC 112-2320-B-030-009 -MY3