A beta dimers differ from monomers in structural propensity, aggregation paths and population of synaptotoxic assemblies

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

Dimers of A beta (amyloid beta-protein) are believed to play an important role in Alzheimer's disease. In the absence of sufficient brain-derived dimers, we studied one of the only possible dimers that could be produced in vivo, [A beta](DiY) (dityrosine cross-linked A beta). For comparison, we used the A beta monomer and a design dimer cross-linked by replacement of Ser(26) with cystine [A beta S26C](2). We showed that similar to monomers, unaggregated dimers lack appreciable structure and fail to alter long-term potentiation. Importantly, dimers exhibit subtly different structural propensities from monomers and each other, and can self-associate to form larger assemblies. Although [A beta](DiY) and [A beta S26C](2) have distinct aggregation pathways, they both populate bioactive soluble assemblies for longer durations than A beta monomers. Our results indicate that the link between A beta dimers and Alzheimer's disease results from the ability of dimers to further assemble and form synaptotoxic assemblies that persist for long periods of time.

Detaljer

Författare
  • Tiernan T. O'Malley
  • Nur Alia Oktaviani
  • Dainan Zhang
  • Aleksey Lomakin
  • Brian O'Nuallain
  • Sara Linse
  • George B. Benedek
  • Michael J. Rowan
  • Frans A. A. Mulder
  • Dominic M. Walsh
Enheter & grupper
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Biokemi och molekylärbiologi

Nyckelord

Originalspråkengelska
Sidor (från-till)413-426
TidskriftBiochemical Journal
Volym461
StatusPublished - 2014
PublikationskategoriForskning
Peer review utfördJa