title: Conformation dependent monoclonal antibodies distinguish different replicating strains or conformers of prefibrillar Aβ oligomers.
abstract: BACKGROUND
  Age-related neurodegenerative diseases share a number of important pathological features, such as accumulation of misfolded proteins as amyloid oligomers and fibrils. Recent evidence suggests that soluble amyloid oligomers and not the insoluble amyloid fibrils may represent the primary pathological species of protein aggregates.
  
  
  RESULTS
  We have produced several monoclonal antibodies that specifically recognize prefibrillar oligomers and do not recognize amyloid fibrils, monomer or natively folded proteins. Like the polyclonal antisera, the individual monoclonals recognize generic epitopes that do not depend on a specific linear amino acid sequence, but they display distinct preferences for different subsets of prefibrillar oligomers. Immunological analysis of a number of different prefibrillar Aβ oligomer preparations show that structural polymorphisms exist in Aβ prefibrillar oligomers that can be distinguished on the basis of their reactivity with monoclonal antibodies. Western blot analysis demonstrates that the conformers defined by the monoclonal antibodies have distinct size distributions, indicating that oligomer structure varies with size. The different conformational types of Aβ prefibrillar oligomers can serve as they serve as templates for monomer addition, indicating that they seed the conversion of Aβ monomer into more prefibrillar oligomers of the same type.
  
  
  CONCLUSIONS
  These results indicate that distinct structural variants or conformers of prefibrillar Aβ oligomers exist that are capable of seeding their own replication. These conformers may be analogous to different strains of prions.
authors.affiliation: Department of Molecular Biology and Biochemistry, University of California, Irvine, CA 92697-3900, USA. cglabe@uci.edu.
authors.forename: Rakez
authors.initials: R
authors.lastname: Kayed
authors.forename: Isabel
authors.initials: I
authors.lastname: Canto
authors.forename: Leonid
authors.initials: L
authors.lastname: Breydo
authors.forename: Suhail
authors.initials: S
authors.lastname: Rasool
authors.forename: Tamas
authors.initials: T
authors.lastname: Lukacsovich
authors.forename: Jessica
authors.initials: J
authors.lastname: Wu
authors.forename: Ricardo
authors.initials: R
authors.lastname: Albay
authors.forename: Anna
authors.initials: A
authors.lastname: Pensalfini
authors.forename: Stephen
authors.initials: S
authors.lastname: Yeung
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Head
authors.forename: J Lawrence
authors.initials: JL
authors.lastname: Marsh
authors.forename: Charles
authors.initials: C
authors.lastname: Glabe