Our observed decreased NAD(P)H and redox ratio with aging and AD may be due to declines in TCA cycle enzymes that generate NADH including pyruvate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, and malate dehydrogenase (Bubber et al., 2005; Yao et al., 2009). This evidence concerns the gene PHGDH and Alzheimer disease.