Systematic analysis of time-dependent neural effects of soluble amyloid β oligomers in culture and in vivo: Prevention by scyllo-inositol.

ABSTRACT: Alzheimer's disease (AD) is currently being addressed by intensive investment in pre-clinical and clinical research on the amyloid hypothesis, but concern remains about the validity of the concept that soluble Aβ oligomers are principally responsible for initiating AD phenotypes. Here, we apply well-defined Aβ oligomers isolated from AD brains or made synthetically to document a systematic accrual of first subtle and then more profound changes in certain synaptic proteins in both primary neuronal cultures and behaving adult mice. Among the first (within hours) synaptic changes are selective decreases in surface levels of certain (e.g., GluA1) but not other (e.g., GluN2B) glutamate receptors and subtle microglial activation. After 4 days, numerous additional synaptic proteins are altered. M

SUBMITTER: Jin M 

PROVIDER: S-EPMC4640956 | biostudies-literature | 2015 Oct

REPOSITORIES: biostudies-literature