Interestingly, Presenilin 1 is also involved in the regulation of PGC-1α expression through the production of APP intracellular domain (AICD) peptide, the APP processing product after γ-secretase cleavage, and PS1-FAD mutations lost the ability to enhance PGC-1α mRNA levels due to the impaired cleavage of APP proteins in AD [163]. The gene discussed is APP; the disease is Alzheimer disease.