Blocking the apolipoprotein E/amyloid β interaction in triple transgenic mice ameliorates Alzheimer's disease related amyloid β and tau pathology

J Neurochem. 2014 Feb;128(4):577-91. doi: 10.1111/jnc.12484. Epub 2013 Nov 6.


Inheritance of the apolipoprotein E4 (apoE4) genotype has been identified as the major genetic risk factor for late-onset Alzheimer's disease (AD). Studies have shown that the binding between apoE and amyloid-β (Aβ) peptides occurs at residues 244-272 of apoE and residues 12-28 of Aβ. ApoE4 has been implicated in promoting Aβ deposition and impairing clearance of Aβ. We hypothesized that blocking the apoE/Aβ interaction would serve as an effective new approach to AD therapy. We have previously shown that treatment with Aβ12-28P can reduce amyloid plaques in APP/PS1 transgenic (Tg) mice and vascular amyloid in TgSwDI mice with congophilic amyloid angiopathy. In the present study, we investigated whether the Aβ12-28P elicits a therapeutic effect on tau-related pathology in addition to amyloid pathology using old triple transgenic AD mice (3xTg, with PS1M146V , APPSwe and tauP30IL transgenes) with established pathology from the ages of 21 to 26 months. We show that treatment with Aβ12-28P substantially reduces tau pathology both immunohistochemically and biochemically, as well as reducing the amyloid burden and suppressing the activation of astrocytes and microglia. These affects correlate with a behavioral amelioration in the treated Tg mice.

Keywords: Alzheimer's disease; Amyloid β; apolipoprotein E; behavior; histochemistry; tau.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / drug therapy*
  • Alzheimer Disease / pathology
  • Alzheimer Disease / psychology
  • Amino Acid Sequence
  • Amyloid beta-Peptides / antagonists & inhibitors*
  • Amyloid beta-Peptides / pharmacology
  • Amyloidosis / drug therapy*
  • Amyloidosis / pathology
  • Amyloidosis / psychology
  • Animals
  • Apolipoproteins E / antagonists & inhibitors*
  • Blotting, Western
  • Brain Chemistry / drug effects
  • Enzyme-Linked Immunosorbent Assay
  • Exploratory Behavior / physiology
  • Gliosis / pathology
  • Immunohistochemistry
  • Maze Learning / drug effects
  • Mice
  • Mice, Transgenic
  • Molecular Sequence Data
  • Motor Activity / physiology
  • Peptide Fragments / pharmacology*
  • Postural Balance / drug effects
  • tau Proteins / metabolism*


  • Amyloid beta-Peptides
  • Apolipoproteins E
  • Peptide Fragments
  • amyloid beta-protein (12-28)
  • tau Proteins