NRF1 and Alzheimer disease: Overexpression of PGC-1α completely rescues, while knockdown of PGC-1α exacerbates impaired mitochondrial biogenesis and deficits in APP mutant M17 cells.445 Interestingly, the mRNA expression levels of CREB, PGC-1α, NRF-1, NRF-2, and TFAM are decreased as early as 1 month of age when there is no significant Aβ oligomer deposition in 3xTg-AD mouse (harboring PS1, APP, and tau human transgenes).