The Concentration of Soluble Extracellular Amyloid-β Protein in Acute Brain Slices from CRND8 Mice

Abstract

BackgroundMany recent studies of the effects of amyloid-β protein (Aβ) on brain tissue from amyloid precursor protein (APP) overexpressing mice have concluded that Aβ oligomers in the extracellular space can profoundly affect synaptic structure and function. As soluble proteins, oliomers of Aβ can diffuse through brain tissue and can presumably exit acute slices, but the rate of loss of Aβ species by diffusion from brain slices and the resulting reduced concentrations of Aβ species in brain slices are unknown.Methodology/Principal FindingsHere I combine measurements of Aβ1–42 diffusion and release from acute slices and simple numerical models to measure the concentration of Aβ1–42 in intact mice (in vivo) and in acute slices from CRND8 mice. The in vivo concentration of diffusible Aβ1–42 in CRND8 mice was 250 pM at 6 months of age and 425 pM at 12 months of age. The concentration of Aβ1–42 declined rapidly after slice preparation, reaching a steady-state concentration within one hour. 50 µm from the surface of an acute slice the steady-state concentration of Aβ was 15–30% of the concentration in intact mice. In more superficial regions of the slice, where synaptic physiology is generally studied, the remaining Aβ is less than 15%. Hence the concentration of Aβ1–42 in acute slices from CRND8 mice is less than 150 pM.Conclusions/SignificanceAβ affects synaptic plasticity in the picomolar concentration range. Some of the effects of Aβ may therefore be lost or altered after slice preparation, as the extracellular Aβ concentration declines from the high picomolar to the low picomolar range. Hence loss of Aβ by diffusion may complicate interpretation of the effects of Aβ in experiments on acute slices from APP overexpressing mice.