PSEN1 and Alzheimer disease: Given the role of ALDH2 as a mitochondrial chaperone to preserve mitochondrial integrity,39 loss of ALDH2 in the APP/PS1 AD model likely results in mtDNA damage and thus cytosolic mtDNA accumulation, which is restored by melatonin-mediated recruitment of ALDH2 to preserve mitochondrial integrity (as evidenced by mitochondrial function and ultrastructure).