Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk

Maria Stefania Spagnuolo, Bernardetta Maresca, Valeria La Marca, Albino Carrizzo, Carlo Veronesi, Chiara Cupidi, Tommaso Piccoli, Raffaele Giovanni Maletta, Amalia Cecilia Bruni, Paolo Abrescia, Luisa Cigliano

Research output: Contribution to journalArticlepeer-review

Abstract

Beta-amyloid accumulation in brain is a driving force for Alzheimer's disease pathogenesis. Apolipoprotein E (ApoE) represents a critical player in beta-amyloid homeostasis, but its role in disease progression is controversial. We previously reported that the acute-phase protein haptoglobin binds ApoE and impairs its function in cholesterol homeostasis. The major aims of this study were to characterize the binding of haptoglobin to beta-amyloid, and to evaluate whether haptoglobin affects ApoE binding to beta-amyloid. Haptoglobin is here reported to form a complex with beta-amyloid as shown by immunoblotting experiments with purified proteins, or by its immunoprecipitation in brain tissues from patients with Alzheimer's disease. The interaction between ApoE and beta-amyloid was previously shown to be crucial for limiting beta-amyloid neurotoxicity and for promoting its clearance. We demonstrate that haptoglobin, rather than impairing ApoE binding to beta-amyloid, promotes to a different extent the formation of the complex between beta-amyloid and ApoE2 or ApoE3 or ApoE4. Our data suggest that haptoglobin and ApoE functions in brain should be evaluated taking into account their mutual interaction with beta-amyloid. Hence, the risk of developing Alzheimer's disease might not only be linked to the different ApoE isoforms, but also rely on the level of critical ligands, such as haptoglobin.

Original languageEnglish
Pages (from-to)837-847
Number of pages11
JournalACS Chemical Neuroscience
Volume5
Issue number9
DOIs
Publication statusPublished - Sep 17 2014

Keywords

  • Alzheimer' disease
  • ApoE/Aβ complex
  • Apolipoprotein E
  • Beta-amyloid
  • Haptoglobin
  • Human brain tissue

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Physiology
  • Cognitive Neuroscience
  • Medicine(all)

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