Besides the general neuroprotective effect observed with caffeine or the use of A2A AR antagonists, caffeine also demonstrated a beneficial effect in specific transgenic mouse models of AD-bearing mutant forms of AβPP and/or presenilin-1 (PS1) [179,180,181], reducing both synapsis loss and neurotoxicity in the hippocampus of rat models [182]. This evidence concerns the gene APP and Alzheimer disease.