Human narcolepsy is linked to degeneration of both locus coeruleus and hypocretin neurons.

Earlier studies led to the conclusion that human narcolepsy with cataplexy was correlated with the loss of hypocretin (Hcrt = orexin) neurons in the hypothalamus. We now report that individuals having narcolepsy with cataplexy also have an average 46% loss in the number and an 18% increase in the size of brainstem norepinephrine neurons in the locus coeruleus (LC), based on our analysis of 11 brains of individuals having narcolepsy with cataplexy. Microglial clustering around Hcrt neurons in the hypothalamus and around noradrenergic neurons in the locus coeruleus of individuals having narcolepsy with cataplexy indicates microglial involvement in the degeneration of both of these neuronal groups.