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

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

SUBMITTER: Kim HY 

PROVIDER: S-EPMC4686862 | biostudies-other | 2015

REPOSITORIES: biostudies-other