Alkaloid caffeine is proved to exert similar activities to melatonin [169] and in its crude form, resulting from decaffeination of coffee, it reduced memory impairment and Aβ1–42 levels in hippocampus of an AD mouse model, the J20 mouse line; crude caffeine maintained mitochondrial function as revealed by increased ATP levels and lower ROS generation and inhibited the apoptosis mediated by mitochondria (reduced caspase-3 activity) [184]. Here, CASP3 is linked to Alzheimer disease.