title: Single particle analysis of tau oligomer formation induced by metal ions and organic solvents.
abstract: Pathological aggregates of tau protein are found in several neurodegenerative diseases termed 'tauopathies'. Increasing evidence indicates that tau oligomer species rather than the large amyloid cytoplasmic inclusions relevant for histopathological diagnosis might be crucial for cellular damage and neurodegeneration. Trivalent metal ions and polyanionic structures like heparin or arachidonic acid have been shown to induce tau aggregation. However, little is known about early processes of tau aggregation. In this study, we applied fluorescence correlation spectroscopy (FCS) and scanning for intensely fluorescent targets (SIFT) to investigate oligomer formation of tau protein at nanomolar protein concentrations at the single-particle level. Our results indicate that the formation of distinct tau oligomers is induced by the trivalent metal ions Fe(3+) and Al(3+) and by organic solvents like DMSO, respectively. In contrast, bivalent metal ions (Cu(2+), Zn(2+), Mn(2+), Ca(2+), Mg(2+)) had no effect. While DMSO-induced small tau oligomers are relatively stable in solution, dynamic remodeling can be initiated by non-ionic detergents. Moreover Al(3+) induces rapid formation of a different oligomer species of larger size. Our results provide further insights into early tau oligomerization and aggregation dynamics.
authors: Zentrum für Neuropathologie und Prionforschung, Ludwig-Maximilians-Universität, München, Germany.
authors: Benedikt
authors: B
authors: Bader
authors: Georg
authors: G
authors: Nübling
authors: Anja
authors: A
authors: Mehle
authors: Simona
authors: S
authors: Nobile
authors: Hans
authors: H
authors: Kretzschmar
authors: Armin
authors: A
authors: Giese
mesh_terms: D002413:Cations, Divalent / Q000737:chemistry; D004121:Dimethyl Sulfoxide / Q000737:chemistry*; D006801:Humans; D008670:Metals / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D012997:Solvents / Q000737:chemistry*; D016875:tau Proteins / Q000737:chemistry* / Q000235:genetics
chemical_list: D002413:Cations, Divalent; D008670:Metals; D012997:Solvents; D016875:tau Proteins; D004121:Dimethyl Sulfoxide