A recent publication suggested that hypocretin (Hcrt, orexin) may mediate the neuropathological process leading to Alzheimer's disease (AD) and that antagonism of hypocretin receptors decreases this process. Narcoleptics have an approximately 90% loss of Hcrt neurons and commensurate reductions in the levels of Hcrt in their cerebrospinal fluid beginning at disease onset, usually before the age of 30. If Hcrt mediates the disease process, narcoleptics should be protected against AD. We examined the postmortem neuropathology and clinical records of 12 sequentially encountered cases of human narcolepsy. We found that AD was present in 4 of these narcoleptics, a prevalence that is similar to that of the general population.