Abstract
Background: Midkine is a heparin-binding cytokine involved in cell survival and various inflammatory processes. Midkine accumulates in senile plaques of patients with Alzheimer’s disease, while it counteracts the cytotoxic effects of amyloid b-peptide and inhibits its oligomerization. The present study was conducted to understand the role of midkine upon plaque formation of amyloid b-peptide.
Methods: A surface plasmon assay was performed to determine the affinity of midkine for amyloid b-peptide. The
deposition of amyloid b-peptide was compared in the brain of wild-type and midkine-deficient mice. An effect of
midkine to microglias was examined by cell migration assay.
Results: Midkine bound to amyloid b-peptide with the affinity of 160 nM. The C-terminal half bound to the
peptide more strongly than the N-terminal half, and heparin inhibited midkine from binding to the peptide.
Pleiotrophin, which has about 50% sequence identity with midkine also bound to amyloid b-peptide. The
deposition of amyloid b-peptide plaques in the cortex and hippocampus was more intense in 15-month-old
midkine-deficient mice, compared to the corresponding wild-type mice. Midkine promoted migration of microglias
in culture.
Conclusions: These results are consistent with the view that midkine attenuates the deposition of amyloid bpeptide plaques, and thus progression of Alzheimer’s disease, by direct binding and also by promoting migration of microglias.