Oligomers of beta-amyloid peptide inhibit BDNF-induced arc expression in cultured cortical Neurons

The progressive memory loss observed in Alzheimer's disease (AD) is accompanied by an increase in the levels of amyloid-beta peptide (Abeta) and a block of synaptic plasticity. Both synaptic plasticity and memory require changes in the expression of synaptic proteins such as the activity-regulated cytoskeleton-associated protein, Arc (also termed Arg3.1). Using a model of synaptic plasticity in which BDNF increases Arc expression in cultured cortical neurons, we have found that an oligomeric form of Abeta strongly inhibits the BDNF-induced increase of Arc expression. Given that Abeta oligomers are likely to be involved in the synaptic dysfunction and cognitive impairment observed in amyloid depositing mouse models, we hypothesize that inhibition of Arc induction by BDNF contributes to the synaptic and memory deficits at early stages of AD.