title: Blocking the apolipoprotein E/amyloid β interaction in triple transgenic mice ameliorates Alzheimer's disease related amyloid β and tau pathology.
abstract: 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.
authors.affiliation: Department of Neurology, New York University School of Medicine, ERSP, New York, NY, USA.
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Ariel
authors.initials: A
authors.lastname: Breitbart
authors.forename: Yanjie
authors.initials: Y
authors.lastname: Sun
authors.forename: Pankaj D
authors.initials: PD
authors.lastname: Mehta
authors.forename: Allal
authors.initials: A
authors.lastname: Boutajangout
authors.forename: Henrieta
authors.initials: H
authors.lastname: Scholtzova
authors.forename: Thomas
authors.initials: T
authors.lastname: Wisniewski
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000686:Amyloidosis / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D000818:Animals; D001057:Apolipoproteins E / Q000037:antagonists & inhibitors*; D015153:Blotting, Western; D001923:Brain Chemistry / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005106:Exploratory Behavior / Q000502:physiology; D005911:Gliosis / Q000473:pathology; D007150:Immunohistochemistry; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008822:Mice, Transgenic; D008969:Molecular Sequence Data; D009043:Motor Activity / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D004856:Postural Balance / Q000187:drug effects; D016875:tau Proteins / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D001057:Apolipoproteins E; D010446:Peptide Fragments; C092395:amyloid beta-protein (12-28); D016875:tau Proteins
keywords: Alzheimer's disease; Amyloid β; apolipoprotein E; behavior; histochemistry; tau