EPPS rescues hippocampus-dependent cognitive deficits in APP/PS1 mice by disaggregation of amyloid-β oligomers and plaques

Alzheimer's disease (AD) is characterized by the transition of amyloid-beta (A beta) monomers into toxic oligomers and plaques. Given that A beta abnormality typically precedes the development of clinical symptoms, an agent capable of disaggregating existing A beta aggregates may be advantageous. Here we report that a small molecule, 4-(2-hydroxyethyl)-1piperazinepropanesulphonic acid (EPPS), binds to A beta aggregates and converts them into monomers. The oral administration of EPPS substantially reduces hippocampus-dependent behavioural deficits, brain A beta oligomer and plaque deposits, glial gamma-aminobutyric acid (GABA) release and brain inflammation in an A beta-overexpressing, APP/PS1 transgenic mouse model when initiated after the development of severe AD-like phenotypes. The ability of EPPS to rescue A beta aggregation and behavioural deficits provides strong support for the view that the accumulation of A beta is an important mechanism underlying AD.