| Summary: | 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.
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