Folate related pathway gene analysis reveals a novel metabolic variant associated with Alzheimer’s disease with a change in metabolic profile.

Metabolic disorders may be important potential causative pathways to Alzheimer’s disease (AD). Cerebrospinal fluid (CSF) decreasing output, raised intracranial pressure and ventricular enlargement have all been linked to AD. Cerebral folate metabolism may be a key player since this is significantly affected by such changes in CSF and genetic susceptibilities may exist in this pathway. In the current study, we aimed to identify whether any single nucleotide polymorphismSNPs) affecting folate and associated metabolic pathways were significantly associated with AD. We took a functional nutrigenomics approach to look for SNPs) in genes for the linked folate, methylation, and biogenic amine neurotransmitter pathways. Changes in metabolism were found with the SNPs identified. An abnormal SNP in methylene tetrahydrofolate dehydrogenase 1 (MTHFD1), was significantly predictive of AD and associated with an increase in tissue glutathione. Individuals without these SNPs had normal levels of glutathione but significantly raised MTHFD1. Both changes would serve to decrease potentially neurotoxic levels of homocysteine. Seven additional genes were associated with Alzheimer’s and five with normal aging MTHFD1 presents a strong prediction of susceptibility and disease among the SNPs associated with AD. Associated physiological changes present potential biomarkers to identify at risk individuals.