APP and Alzheimer disease: In the brain tissue samples from APPswe/PS1dE9 (APP/PS1) transgenic mouse model and AD patients, expression levels of genes necessary to mitochondrial replication and energy metabolism, including the peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), and neurogenic differentiation factor-6 (NEUROD6), are significantly downregulated [135, 136], indicating a pronounced mtDNA maintenance defect in AD.