Melatonin is synthesized in the pineal gland, retina, and organs. Melatonin has a variety of physiological functions on free radicals, circadian rhythms, immune system. In addition, melatonin is relevant for various pathologies in central nervous system disorders such as cerebral ischemia and Alzheimer’s disease (AD). Particularly, AD has hallmarks including both aggregation of senile plaques derived from amyloid beta peptides and neurofibrillary tangles, especially in hippocampus or cerebral cortex relevant to learning and memory. In addition, insulin signal dysfunction resulted in cognitive decline is a typical pathology in AD brain. Decreased melatonin in cerebrospinal
fluid is observed in AD patients. Melatonin has the ability to regulate amyloid precursor protein metabolism and prevent Aβ pathology. Moreover, melatonin is involved in insulin secretion in animals and humans and melatonin receptor deficiency influences insulin resistance in brain. In conclusion, melatonin contributes to improvement of learning and memory processing in AD. Thus, melatonin may serve as a potential therapeutic factor for cognitive decline in AD. Here, we aim to summarize recent studies that suggest the relationship between melatonin and cognitive impairment in AD.