Amyloid-beta protein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory.

ABSTRACT: Alzheimer's disease constitutes a rising threat to public health. Despite extensive research in cellular and animal models, identifying the pathogenic agent present in the human brain and showing that it confers key features of Alzheimer's disease has not been achieved. We extracted soluble amyloid-beta protein (Abeta) oligomers directly from the cerebral cortex of subjects with Alzheimer's disease. The oligomers potently inhibited long-term potentiation (LTP), enhanced long-term depression (LTD) and reduced dendritic spine density in normal rodent hippocampus. Soluble Abeta from Alzheimer's disease brain also disrupted the memory of a learned behavior in normal rats. These various effects were specifically attributable to Abeta dimers. Mechanistically, metabotropic glutamate receptors wer

SUBMITTER: Shankar GM 

PROVIDER: S-EPMC2772133 | biostudies-literature | 2008 Aug

REPOSITORIES: biostudies-literature