Dextran sulfate sodium inhibits amyloid-ß oligomer binding to cellular prion protein.

Amyloid-ß peptide (Aß), especially its oligomeric form, is believed to play an important role in the pathogenesis of Alzheimer's disease (AD). To this end, the binding of Aß oligomer to cellular prion protein (PrP(C)) plays an important role in synaptic dysfunction in a mouse model of AD. Here, we have screened for compounds that inhibit Aß oligomer binding to PrP(C) from medicines already used clinically (Mizushima Approved Medicine Library 1), and identified dextran sulfate sodium (DSS) as a candidate. In a cell-free assay, DSS inhibited Aß oligomer binding to PrP(C) but not to ephrin receptor B2, another endogenous receptor for Aß oligomers, suggesting that the drug's action is specific to the binding of Aß oligomer to PrP(C) . Dextran on the other hand did not affect this binding. DSS also suppressed Aß oligomer binding to cells expressing PrP(C) but not to control cells. Furthermore, while incubation of mouse hippocampal slices with Aß oligomers inhibited the induction of long-term potentiation, simultaneous treatment with DSS restored the long-term potentiation. As DSS has already been approved for use in patients with hypertriglyceridemia, and its safety in humans has been confirmed, we propose further analysis of this drug as a candidate for AD treatment. Amyloid-ß peptide (Aß) oligomer-binding to cellular prion protein (PrP(C) ) is important in synaptic dysfunction in Alzheimer's disease (AD). We found here that dextran sulfate sodium (DSS) inhibits Aß oligomer binding to PrP(C) . Simultaneous treatment of hippocampal slices with DSS restored long-term potentiation (LTP) in the presence of Aß oligomers. Since DSS has already been approved for clinical use, we propose this drug is a candidate drug for AD treatment.