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

Background: Many recent studies of the effects of amyloid-beta protein (A beta) on brain tissue from amyloid precursor protein (APP) overexpressing mice have concluded that A beta oligomers in the extracellular space can profoundly affect synaptic structure and function. As soluble proteins, oliomers of A beta can diffuse through brain tissue and can presumably exit acute slices, but the rate of loss of A beta species by diffusion from brain slices and the resulting reduced concentrations of A beta species in brain slices are unknown. Methodology/Principal Findings: Here I combine measurements of A beta 1-42 diffusion and release from acute slices and simple numerical models to measure the concentration of A beta 1-42 in intact mice (in vivo) and in acute slices from CRND8 mice. The in vivo concentration of diffusible A beta 1-42 in CRND8 mice was 250 pM at 6 months of age and 425 pM at 12 months of age. The concentration of A beta 1-42 declined rapidly after slice preparation, reaching a steady-state concentration within one hour. 50 mm from the surface of an acute slice the steady-state concentration of A beta was 15-30% of the concentration in intact mice. In more superficial regions of the slice, where synaptic physiology is generally studied, the remaining A beta is less than 15%. Hence the concentration of A beta 1-42 in acute slices from CRND8 mice is less than 150 pM. Conclusions/Significance: A beta affects synaptic plasticity in the picomolar concentration range. Some of the effects of A beta may therefore be lost or altered after slice preparation, as the extracellular A beta concentration declines from the high picomolar to the low picomolar range. Hence loss of A beta by diffusion may complicate interpretation of the effects of A beta in experiments on acute slices from APP overexpressing mice.