Conversely, NR supplementation also can increase NAD+ levels in brain NR and has been evaluated in AD models, resulting in attenuation of cognitive impairment in vivo by increasing levels of PGC1a, which in turn is associated with the prevention of amyloid-β production [178], suggesting that SIRT1-mediated activation of PGC1a must be involved. The gene discussed is SIRT1; the disease is Alzheimer disease.