Wake-active neurons across aging and neurodegeneration: a potential role for sleep disturbances in promoting disease

Sleep/wake disturbance is a feature of almost all common age-related neurodegenerative diseases. Although the reason for this is unknown, it is likely that this inability to maintain sleep and wake states is in large part due to declines in the number and function of wake-active neurons, populations of cells that fire only during waking and are silent during sleep. Consistent with this, many of the brain regions that are most susceptible to neurodegeneration are those that are necessary for wake maintenance and alertness. In the present review, these wake-active populations are systematically assessed in terms of their observed pathology across aging and several neurodegenerative diseases, with implications for future research relating sleep and wake disturbances to aging and age-related neurodegeneration.