Diurnal choroid plexus function in mice depends on sex, age, and amyloid-β status

The adult choroid plexus (ChP) produces the majority of cerebrospinal fluid (CSF), yet little is known about the biological and physiological factors that regulate the ChP under healthy conditions. CSF physiology is regulated by sleep and/or time of day and alters with age and in Alzheimer’s disease (AD), where sleep and circadian disruption often co-occur. We compare the transcriptome from mouse ChP in three conditions (young, aged, aged with amyloid β (Aβ) pathology) collected at day and night. In young mice, diurnal ChP gene expression changes are reflected in ontology pathways for protein stability and cell metabolism. In aged mice, these pathways shift to membrane transport and ion homeostasis, with diurnal regulation lost with Aβ pathology. ChP protein expression of ion co-transporter NKCC1 varies across diurnal timepoints with both age and sex and accompanies changes in CSF [K+]. Together, our work suggests an interplay between diurnal regulation of membrane transport in the ChP and CSF ion composition may shed light on the role of CSF dynamics in brain function and age-related pathological processes. Diurnal regulation of the choroid plexus in mice is age- and sex-dependent and is disrupted by amyloid pathology, with altered NKCC1 expression and cerebrospinal fluid K⁺ homeostasis, implicating circadian control of cerebrospinal fluid dynamics in brain aging.