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.
authors: ISPAAM, Consiglio Nazionale delle Ricerche, via Argine 1085, 80147 Napoli, Italia.
authors: Maria Stefania
authors: MS
authors: Spagnuolo
authors: Bernardetta
authors: B
authors: Maresca
authors: Valeria
authors: V
authors: La Marca
authors: Albino
authors: A
authors: Carrizzo
authors: Carlo
authors: C
authors: Veronesi
authors: Chiara
authors: C
authors: Cupidi
authors: Tommaso
authors: T
authors: Piccoli
authors: Raffaele Giovanni
authors: RG
authors: Maletta
authors: Amalia Cecilia
authors: AC
authors: Bruni
authors: Paolo
authors: P
authors: Abrescia
authors: Luisa
authors: L
authors: Cigliano
mesh_terms: D000328:Adult; D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000235:genetics / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D016466:CHO Cells; D003412:Cricetulus; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006242:Haptoglobins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D014162:Transfection
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D001057:Apolipoproteins E; D006242:Haptoglobins
keywords: Alzheimer’disease; ApoE/Aβ complex; Beta-amyloid; apolipoprotein E; haptoglobin; human brain tissue