The Amyloid β Peptide (Aβ1 - 40) Is Thermodynamically Soluble at Physiological Concentrations

Precipitation of the 39−43-residue amyloid β peptide (Aβ) is a crucial factor in Alzheimer's disease (AD). In normal as well as in AD-afflicted brain, the Aβ concentration is estimated to be a few nanomolar. Here we show that Aβ1 - 40 precipitates in vitro only if the dissolved concentration is >14 μM. Using fluorescence correlation spectroscopy, we further show that the precipitation is complete in 1 day, after which the size distribution of Aβ monomer/oligomers in the solution phase becomes stationary in time and independent of the starting Aβ concentration. Mass spectra confirm that both the solution phase and the coexisting precipitate contain chemically identical Aβ molecules. Incubation at 68 °C for 1 h reduces the solubility by