Aβ-globulomers are formed independently of the fibril pathway

• Main Authors: Gerald P. Gellermann, Helga Byrnes, Andreas Striebinger, Kathrin Ullrich, Reinhold Mueller, Heinz Hillen, Stefan Barghorn
• Format: Article
• Language: English
• Published: Elsevier 2008-05-01
• Series: Neurobiology of Disease
• Subjects: Alzheimer's disease; Dementia, Amyloid β-protein; Oligomers; Fibrils; Conformational diseases; Monocyte
• Online Access: http://www.sciencedirect.com/science/article/pii/S0969996108000090

Soluble Aβ-oligomers are currently discussed as the major causative species for the development of Alzheimer's disease (AD). Consequently, the β-amyloid cascade hypothesis was extended by Aβ-oligomers and their central neuropathogenic role in AD. However, the molecular structure of Aβ-oligomers and their relation to amyloid fibril formation remains elusive. Previously we demonstrated that incubation of Aβ1–42 with SDS or fatty acids induces the formation of a homogeneous globular Aβ-oligomer termed Aβ-globulomer. In this study we investigated the role of Aβ-globulomers in the aggregation pathway of Aβ-peptide. We used in vitro assays such as thioflavin-T binding and aggregation inhibitors like Congo red to reveal that Aβ-peptide in its Aβ-globulomer conformation is a structural entity which is independent from amyloid fibril formation. In addition, cellular Alzheimer's-like plaque forming assays show the resistance of Aβ-globulomers to deposition as amyloid plaques. We hypothesize that a conformational switch of Aβ is decisive for either fibril formation or alternatively and independently Aβ-globulomer formation.