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 journalArticle

13 Citations (Scopus)

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

Fingerprint

Haptoglobins
Apolipoproteins
Crosstalk
Amyloid
Apolipoproteins E
Brain
Alzheimer Disease
Homeostasis
Apolipoprotein E2
Apolipoprotein E3
Apolipoprotein E4
Acute-Phase Proteins
Immunoprecipitation
Immunoblotting
Disease Progression
Protein Isoforms
Cholesterol
Tissue
Ligands

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)

Cite this

Spagnuolo, M. S., Maresca, B., La Marca, V., Carrizzo, A., Veronesi, C., Cupidi, C., ... Cigliano, L. (2014). Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk. ACS Chemical Neuroscience, 5(9), 837-847. https://doi.org/10.1021/cn500099f

Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk. / Spagnuolo, Maria Stefania; Maresca, Bernardetta; La Marca, Valeria; Carrizzo, Albino; Veronesi, Carlo; Cupidi, Chiara; Piccoli, Tommaso; Maletta, Raffaele Giovanni; Bruni, Amalia Cecilia; Abrescia, Paolo; Cigliano, Luisa.

In: ACS Chemical Neuroscience, Vol. 5, No. 9, 17.09.2014, p. 837-847.

Research output: Contribution to journalArticle

Spagnuolo, MS, Maresca, B, La Marca, V, Carrizzo, A, Veronesi, C, Cupidi, C, Piccoli, T, Maletta, RG, Bruni, AC, Abrescia, P & Cigliano, L 2014, 'Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk', ACS Chemical Neuroscience, vol. 5, no. 9, pp. 837-847. https://doi.org/10.1021/cn500099f
Spagnuolo, Maria Stefania ; Maresca, Bernardetta ; La Marca, Valeria ; Carrizzo, Albino ; Veronesi, Carlo ; Cupidi, Chiara ; Piccoli, Tommaso ; Maletta, Raffaele Giovanni ; Bruni, Amalia Cecilia ; Abrescia, Paolo ; Cigliano, Luisa. / Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk. In: ACS Chemical Neuroscience. 2014 ; Vol. 5, No. 9. pp. 837-847.
@article{81fb92ee78cb4aa2855a741a08fc2049,
title = "Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk",
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.",
keywords = "Alzheimer' disease, ApoE/Aβ complex, Apolipoprotein E, Beta-amyloid, Haptoglobin, Human brain tissue",
author = "Spagnuolo, {Maria Stefania} and Bernardetta Maresca and {La Marca}, Valeria and Albino Carrizzo and Carlo Veronesi and Chiara Cupidi and Tommaso Piccoli and Maletta, {Raffaele Giovanni} and Bruni, {Amalia Cecilia} and Paolo Abrescia and Luisa Cigliano",
year = "2014",
month = "9",
day = "17",
doi = "10.1021/cn500099f",
language = "English",
volume = "5",
pages = "837--847",
journal = "ACS Chemical Neuroscience",
issn = "1948-7193",
publisher = "American Chemical Society",
number = "9",

}

TY - JOUR

T1 - Haptoglobin interacts with Apolipoprotein e and beta-amyloid and influences their crosstalk

AU - Spagnuolo, Maria Stefania

AU - Maresca, Bernardetta

AU - La Marca, Valeria

AU - Carrizzo, Albino

AU - Veronesi, Carlo

AU - Cupidi, Chiara

AU - Piccoli, Tommaso

AU - Maletta, Raffaele Giovanni

AU - Bruni, Amalia Cecilia

AU - Abrescia, Paolo

AU - Cigliano, Luisa

PY - 2014/9/17

Y1 - 2014/9/17

N2 - 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.

AB - 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.

KW - Alzheimer' disease

KW - ApoE/Aβ complex

KW - Apolipoprotein E

KW - Beta-amyloid

KW - Haptoglobin

KW - Human brain tissue

UR - http://www.scopus.com/inward/record.url?scp=84923361440&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923361440&partnerID=8YFLogxK

U2 - 10.1021/cn500099f

DO - 10.1021/cn500099f

M3 - Article

C2 - 25058565

AN - SCOPUS:84923361440

VL - 5

SP - 837

EP - 847

JO - ACS Chemical Neuroscience

JF - ACS Chemical Neuroscience

SN - 1948-7193

IS - 9

ER -