Trace copper(II) or zinc(II) ions drastically modify the aggregation behavior of amyloid-beta1-42: an AFM study.
Formation of amyloid-beta (Abeta){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 Abeta {1-42} 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.
Innocenti
Massimo
M
Department of Chemistry, University of Florence, Sesto Fiorentino, Italy. m.innocenti@unifi.it
Salvietti
Emanuele
E
Guidotti
Martina
M
Casini
Angela
A
Bellandi
Silvano
S
Foresti
Maria Luisa
ML
Gabbiani
Chiara
C
Pozzi
Andrea
A
Zatta
Paolo
P
Messori
Luigi
L
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D003300:Copper / Q000378:metabolism*; D006801:Humans; D007477:Ions / Q000378:metabolism; D018625:Microscopy, Atomic Force; D010446:Peptide Fragments / Q000378:metabolism*; D015032:Zinc / Q000378:metabolism*
D016229:Amyloid beta-Peptides; D007477:Ions; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D003300:Copper; D015032:Zinc