MTHFR and Alzheimer disease: Importantly for our hypothesis, 2 folate-related genes were found to be significantly associated with AD, methylene tetrahydrofolate dehydrogenase 1 (MTHFD1) and methylene tetrahydrofolate reductase (MTHFR), with MTHFD1 significant on all tests and MTHFR significant only on a Chi, Squared test in which positive and neutral variants were grouped and tested against negative variants.