Mitochondrial biogenesis plays an essential role in maintaining functional neuronal mitochondrial mass by compensating for damaged mitochondria and is thought to be impaired in AD, where the levels of nuclear respiratory factor 1 (Nrf1), nuclear respiratory factor 1 (Nrf2), and mitochondrial transcription factor A (TFAM) along with nuclear levels of peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α) are reduced in the hippocampus. The gene discussed is TFAM; the disease is Alzheimer disease.