Amyloid-β: Acute-phase apolipoprotein with metal-binding activity

Issue title: Dedicated to Prof. Marino Nicolini

Article type: Research Article

Authors: Kontush, Anatol

Affiliations: INSERM Unité 551, Hôpital de la Pitié, Pavillon Benjamin Delessert, 83, Bd de l'Hôpital, 75651 Paris Cedex 13, France. E-mail: [email protected]

Abstract: In monomeric form, amyloid-β (Aβ), an amphipatic 4 kDa peptide which plays a key role in the pathogenesis of Alzheimer's disease (AD), is associated with lipoproteins in biological fluids and possesses high affinity to transition metal ions; in addition, synthesis of Aβ is upregulated under acute phase conditions. These data suggest that Aβ can be regarded as a normal physiological component of lipoproteins and may represent an acute-phase apolipoprotein with metal-binding activity. Interaction with transition metal ions may cause aggregation of Aβ, leading to formation of oligomers. Such oligomerised Aβ may lose its normal biological functions and acquire deleterious activities. To be efficient, novel anti-AD therapies should target oligomeric forms of Aβ while preserving the monomeric form of the peptide.

Keywords: Alzheimer's disease, amyloid-β, apolipoproteins, lipoproteins, lipids, transition metals, oxidation, antioxidants

DOI: 10.3233/JAD-2005-8205

Journal: Journal of Alzheimer's Disease, vol. 8, no. 2, pp. 129-137, 2005