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

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.