The Choroid Plexus Removes β-Amyloid from Brain Cerebrospinal Fluid

Abstract

β-Amyloid (Aβ) concentration in the cerebrospinal fluid (CSF) of the brain may be regulated by the choroid plexus, which forms a barrier between blood and brain CSF. Aβ uptake from CSF was determined as its volume of distribution (V_D) into isolated rat choroid plexus tissue. The V_D of [¹²⁵l]Aβ_1–40 was corrected by subtraction of the V_D of [¹⁴C]sucrose, a marker for extracellular space and diffusion. Aβ uptake into choroid plexus was time and temperature dependent. Uptake of [¹²⁵l]Aβ was saturable. Aβ uptake was not affected by addition of transthyretin or apolipoprotein E3. In studies with primary culture monolayers of choroidal epithelial cells in Transwells, Aβ permeability across cells, corrected by [¹⁴C]sucrose, was greater from the CSF-facing membrane than from the blood-facing membrane. Similarly, cellular accumulation of [¹²⁵l]Aβ was concentrative from both directions and was greater from the CSF-facing membrane, suggesting a bias for efflux. Overall, these results suggest the choroid plexus selectively cleanses Aβ from the CSF by an undetermined mechanism(s), potentially reducing Aβ from normal brains and the brains of Alzheimer's disease patients.