Alzheimers disease (AD) is the most frequent cause of late-life dementia, with pathological characteristics of extracellular aggregation of amyloid b-peptides (Abs) with 39 ± 43 amino acids, which are proteolytically derived from the transmembrane amyloid precursor protein (APP). [1] Recent studies indicate that the amyloid b-peptide(1 ± 42) (Ab( 42)) plays a central role in the formation of the b-amyloid fibril (fAb) in vivo among the different coexisting Ab species. [2] Further elucidation of the mechanism of Ab(42) aggregation, and the effect of extrinsic or environmental factors such as pH, metal ions, ionic strength, membrane-like surfaces, and solvent hydrophobicity on the aggregation is useful for our understanding of the pathophysiology and treatment of Alzheimers disease and other similar neurodegenerative diseases.
Some metal ions such as Zn 2 , Cu 2 , etc., are essential in trace amounts with important fundamental roles in the biochemistry of human life. [3] It was recently reported that Cu 2 , Zn 2 , and Fe 3 are concentrated in the normal neocortex. The concentrations of these cations are more than doubled in the cerebral amyloid deposits of AD brains compared with the neuropil of normal age-matched brains. [4] However, the role of Cu 2 in neurodegenerative diseases such as Alzheimers disease is still not clear, although the effect of Zn 2 on the aggregation of Abs has been demonstrated by several groups in recent years. [5] Our recent study indicated that the complexation of peptides with Cu 2 is responsible for inducing and enhancing the formation of the a-helix conformation of the alanine-based peptides with a Trp/His pair in different geometrical spacings and positions. [6] Herein we describe the aggregation of Ab(42) and demonstrate for the first time that Cu 2 inhibits the aggregation of Ab(42) with both thioflavin T (ThT) fluorescence assay and atomic force microscopy (AFM) in vitro.