Inhibition of Aβ fibril formation and Aβ-induced cytotoxicity by senile plaque-associated proteins

Aβ neurotoxicity is generally believed to require Aβ fibril formation. The prevention of Aβ fibril formation thus seems to be a promising strategy for the treatment of AD. Recent studies have shown senile plaque-associated proteins such as laminin to have an inhibitory effect on both Aβ40 and Aβ42 fibril formation in vitro. In the present study, we thus investigated whether or not midkine (MK) and α2-macroglobulin (α2M), both of which are also senile plaque-associated proteins like laminin, affect Aβ fibril formation and Aβ-induced cytotoxicity. The present study demonstrated that both MK and α2M inhibit both Aβ fibril formation and Aβ-induced cytotoxicity in PC12 cells. The confirmation of the present results based on in vivo experiments is called for in future studies to clarify whether or not senile plaque-associated proteins such as MK and α2M can be a model for therapeutic agents in the treatment of AD.