Significantly, we demonstrate in vivo that severe MTHFR deficiency is associated with down regulation of LCMT1 and PP2A/Bα, and concomitant enhancement of Tau phosphorylated at the AD-like PHF-1 epitope in the hippocampus and cerebellum, and to a lesser extent in the cortex. The gene discussed is MTHFR; the disease is Alzheimer disease.