Age, Sex Hormones, and Circadian Rhythm Regulate the Expression of Amyloid-Beta Scavengers at the Choroid Plexus

Abstract

Accumulation of amyloid-beta (A beta) in the brain is thought to derive from the impairment of A beta clearance mechanisms rather than from its overproduction, which consequently contributes to the development of Alzheimer's disease. The choroid plexus epithelial cells constitute an important clearance route for A beta, either by facilitating its transport from the cerebrospinal fluid to the blood, or by synthesizing and secreting various proteins involved in A beta degradation. Impaired choroid plexus synthesis, secretion, and transport of these A beta-metabolizing enzymes have been therefore associated with the disruption of A beta homeostasis and amyloid load. Factors such as aging, female gender, and circadian rhythm disturbances are related to the decline of choroid plexus functions that may be involved in the modulation of A beta-clearance mechanisms. In this study, we investigated the impact of age, sex hormones, and circadian rhythm on the expression of A beta scavengers such as apolipoprotein J, gelsolin, and transthyretin at the rat choroid plexus. Our results demonstrated that mRNA expression and both intracellular and secreted protein levels of the studied A beta scavengers are age-, sex-, and circadian-dependent. These data suggest that the A beta-degradation and clearance pathways at the choroid plexus, mediated by the presence of A beta scavengers, might be compromised as a consequence of aging and circadian disturbances. These are important findings that enhance the understanding of A beta-clearance-regulating mechanisms at the blood-cerebrospinal fluid barrier.