Recently, severe brain malformations with pyruvate dehydrogenase deficiency and DS were reported (61), and the Down syndrome critical region 2 protein was shown to inhibit the transcriptional activity of PPARβ in a cell line, indicating a potential dysfunction of PPAR activation in DS, in which hAPP expression level is increased (62). The gene discussed is PPARD; the disease is pyruvate dehydrogenase deficiency.