Abstract

The progressive memory loss observed in Alzheimers disease (AD) is accompanied by an increase in the levels of amyloid-β peptide (Aβ) 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 Aβ strongly inhibits the BDNF-induced increase of Arc expression. Given that Aβ 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.

Keywords: Synaptic plasticity, Arg3.1, Arc, Alzheimer's disease, LTP, BDNE