title: Interactions between amyloid-β and Tau fragments promote aberrant aggregates: implications for amyloid toxicity.
abstract: We have investigated at the oligomeric level interactions between Aβ(25-35) and Tau(273-284), two important fragments of the amyloid-β and Tau proteins, implicated in Alzheimer's disease. We are able to directly observe the coaggregation of these two peptides by probing the conformations of early heteroligomers and the macroscopic morphologies of the aggregates. Ion-mobility experiment and theoretical modeling indicate that the interactions of the two fragments affect the self-assembly processes of both peptides. Tau(273-284) shows a high affinity to form heteroligomers with existing Aβ(25-35) monomer and oligomers in solution. The configurations and characteristics of the heteroligomers are determined by whether the population of Aβ(25-35) or Tau(273-284) is dominant. As a result, two types of aggregates are observed in the mixture with distinct morphologies and dimensions from those of pure Aβ(25-35) fibrils. The incorporation of some Tau into β-rich Aβ(25-35) oligomers reduces the aggregation propensity of Aβ(25-35) but does not fully abolish fibril formation. On the other hand, by forming complexes with Aβ(25-35), Tau monomers and dimers can advance to larger oligomers and form granular aggregates. These heteroligomers may contribute to toxicity through loss of normal function of Tau or inherent toxicity of the aggregates themselves.
authors.affiliation: Department of Chemistry and Biochemistry and ‡Department of Physics, University of California , Santa Barbara, California 93106, United States.
authors.forename: Thanh D
authors.initials: TD
authors.lastname: Do
authors.forename: Nicholas J
authors.initials: NJ
authors.lastname: Economou
authors.forename: Ali
authors.initials: A
authors.lastname: Chamas
authors.forename: Steven K
authors.initials: SK
authors.lastname: Buratto
authors.forename: Joan-Emma
authors.initials: JE
authors.lastname: Shea
authors.forename: Michael T
authors.initials: MT
authors.lastname: Bowers
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism* / Q000633:toxicity; D018625:Microscopy, Atomic Force; D008958:Models, Molecular; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D016875:tau Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016229:Amyloid beta-Peptides; D016875:tau Proteins