Trace Copper(II) or Zinc(II) Ions Drastically Modify the Aggregation Behavior of Amyloid-β_1–42: An AFM Study

Article type: Research Article

Authors: Innocenti, Massimo^{a; *} | Salvietti, Emanuele^a | Guidotti, Martina^a | Casini, Angela^c | Bellandi, Silvano^a | Foresti, Maria Luisa^a | Gabbiani, Chiara^a | Pozzi, Andrea^a | Zatta, Paolo^b | Messori, Luigi^{a; *}

Affiliations: [a] Department of Chemistry, University of Florence, Sesto Fiorentino, Italy | [b] CNR-Institute for Biomedical Technologies, Padova “Metalloproteins” Unit, Department of Biology, University of Padova, Padova, Italy | [c] Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), Lausanne, Switzerland

Correspondence: [*] Correspondence to: Dr. Massimo Innocenti, E-mail: [email protected] and Prof. Luigi Messori, E-mail: [email protected], Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino, Italy. Fax: +39 055 457 3385.

Abstract: Formation of amyloid-β (Aβ)1–42 amyloid fibrils, a characteristic feature of Alzheimer's disease (AD), was monitored in situ through atomic force microscopy (AFM). Well-structured amyloid fibrils slowly formed in solution within 24 hours for which high quality AFM pictures could be obtained. Remarkably, addition of either copper(II) or zinc(II) ions to the incubation medium, even at extremely low molar ratios, dramatically changed the Aβ1–42 aggregation profile and prevented fibril formation. Aggregates of different morphology appeared in accordance with previous observations: small globular aggregates upon addition of zinc; ill-structured micro-aggregates in the case of copper. The implications of these AFM results are discussed in the context of current concepts for AD metallobiology.

Keywords: Alzheimer's disease, amyloid-β, atomic force microscopy, metal ions

DOI: 10.3233/JAD-2010-1338

Journal: Journal of Alzheimer's Disease, vol. 19, no. 4, pp. 1323-1329, 2010