Diurnal and seasonal molecular rhythms in the human brain and their relation to Alzheimer disease.

Diurnal and seasonal rhythms influence many aspects of human physiology including brain function. Moreover, altered diurnal and seasonal behavioral and physiological rhythms have been linked to Alzheimer's disease and related dementias (ADRD). Understanding the molecular basis for these links may lead to identification of novel targets to mitigate the negative impact of normal and abnormal diurnal and seasonal rhythms on ADRD or to alleviate the adverse consequences of ADRD on normal diurnal and seasonal rhythms. Diurnally and seasonally rhythmic gene expression and epigenetic modification in the human neocortex may be a key mechanism underlying these links. This chapter will first review the observed epidemiological links between normal and abnormal diurnal and seasonal rhythmicity, cognitive impairment, and ADRD. Then it will review normal diurnal and seasonal rhythms of brain epigenetic modification and gene expression in model organisms. Finally, it will review evidence for diurnal and seasonal rhythms of epigenetic modification and gene expression the human brain in aging, Alzheimer's disease, and other brain disorders.