Alzheimer's Aβ interacts with cellular prion protein inducing neuronal membrane damage and synaptotoxicity

A major feature of Alzheimer's disease is the accumulation of β-amyloid (Aβ) peptide in the brain. Recent studies have indicated that Aβ oligomers (Aβo) can interact with the cellular Prion Protein (PrPc). Therefore, this interaction might be driving some of Aβ toxic effects in the synaptic region. In the present study, we report that Aβo binds to PrPc in the neuronal membrane playing a role on toxic effects induced by Aβ. Phospholipase C-enzymatic cleavage of PrPc from the plasma membrane attenuated the association of Aβo to the neurons. Furthermore, an anti-PrP antibody (6D11) decreased the association of Aβo to hippocampal neurons with a concomitant reduction in Aβo and PrPc co-localization. Interestingly, this antibody blocked the increase in membrane conductance and intracellular calcium induced by Aβo. Thus, the data indicate that PrPc plays a role on the membrane perforations produced by Aβo, the increase in calcium ions and the release of synaptic vesicles that subsequently leads to synaptic failure. Future studies blocking Aβo interaction with PrPc could be important for the discovery of new therapeutic strategies for Alzheimer's disease.

Alzheimer; Beta amyloid; Prion; Synaptic toxicity.