title: Midkine as a factor to counteract the deposition of amyloid β-peptide plaques: in vitro analysis and examination in knockout mice.
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 β-peptide and inhibits its oligomerization. The present study was conducted to understand the role of midkine upon plaque formation of amyloid β-peptide.
  
  
  METHODS
  A surface plasmon assay was performed to determine the affinity of midkine for amyloid β-peptide. The deposition of amyloid β-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 β-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 β-peptide. The deposition of amyloid β-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 β-peptide plaques, and thus progression of Alzheimer's disease, by direct binding and also by promoting migration of microglias.
authors.affiliation: Department of Biochemistry, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. hmurama@dpc.agu.ac.jp.
authors.forename: Hisako
authors.initials: H
authors.lastname: Muramatsu
authors.forename: Katsunori
authors.initials: K
authors.lastname: Yokoi
authors.forename: Lan
authors.initials: L
authors.lastname: Chen
authors.forename: Keiko
authors.initials: K
authors.lastname: Ichihara-Tanaka
authors.forename: Terutoshi
authors.initials: T
authors.lastname: Kimura
authors.forename: Takashi
authors.initials: T
authors.lastname: Muramatsu