Spontaneous in vitro formation of supramolecular beta-amyloid structures, "betaamy balls", by beta-amyloid 1-40 peptide.
The concentration of beta-amyloid peptide (Abeta), x-42 or x-40 amino acids long, increases in brain with the progression Alzheimer's disease (AD). These peptides are deposited extracellularly as highly insoluble fibrils that form densities of amyloid plaques. Abeta fibrillization is a complex polymerization process preceded by the formation of oligomeric and prefibrillar Abeta intermediates. In some of our in vitro studies, in which the kinetics of intermediate steps of fibril formation were examined, we used concentrations of synthetic Abeta that exceed what is normally employed in fibrillization studies, 300-600 microM. At these concentrations, in a cell free system and under physiological conditions, Abeta 1-40 peptide (Abeta40) forms fibrils that spontaneously assemble into clearly defined spheres, "betaamy balls", with diameters of approximately 20-200 microm. These supramolecular structures show weak birefringence with Congo red staining and high stability with prolonged incubation times (at least 2 weeks) at 30 degrees C, freezing, and dilution in H(2)O. At 600 microM, they are detected after incubation for approximately 20 h. Abeta peptide 1-42 (Abeta42) lacks the ability to form betaamy balls but accelerates Abeta40 betaamy ball formation at low stoichiometric levels (1:20 Abeta42:Abeta40 ratio). Abeta42 levels above this (=10-50% w/w) impede Abeta40 betaamy ball formation. Using light (LM) and electron microscopy (EM), this study examines the gross morphology and ultrastructure of Abeta40 betaamy balls and their time course of formation, in the absence and presence of Abeta42, along with some stability measures. As spheres of a misfolded protein, betaamy balls resemble both AD Abeta senile plaques and neuronal inclusion bodies associated with other neurodegenerative diseases.
Westlind-Danielsson
A
A
NEUROTEC, Karolinska Institute, Geriatric Medicine, Novum, KFC, S-141 86 Huddinge, Sweden. Anita.Westlind-Danielsson@neurotec.ki.se
Arnerup
G
G
D000544:Alzheimer Disease / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D001923:Brain Chemistry; D006801:Humans; D010446:Peptide Fragments / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D058225:Plaque, Amyloid / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D017434:Protein Structure, Tertiary
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011108:Polymers; C078592:amyloid beta-protein (1-40)