% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{Dammers:836944,
      author       = {Dammers, C. and Schwarten, M. and Buell, A. K. and
                      Willbold, Dieter},
      title        = {{P}yroglutamate-modified {A}β(3-42) affects aggregation
                      kinetics of {A}β(1-42) by accelerating primary and
                      secondary pathways},
      journal      = {Chemical science},
      volume       = {8},
      number       = {7},
      issn         = {2041-6539},
      address      = {Cambridge},
      publisher    = {RSC},
      reportid     = {FZJ-2017-05969},
      pages        = {4996 - 5004},
      year         = {2017},
      abstract     = {The aggregation into amyloid fibrils of amyloid-β (Aβ)
                      peptides is a hallmark of Alzheimer's disease. A variety of
                      Aβ peptides have been discovered in vivo, with
                      pyroglutamate-modified Aβ (pEAβ) forming a significant
                      proportion. pEAβ is mainly localized in the core of
                      plaques, suggesting a possible role in inducing and
                      facilitating Aβ oligomerization and accumulation. Despite
                      this potential importance, the aggregation mechanism of
                      pEAβ and its influence on the aggregation kinetics of other
                      Aβ variants have not yet been elucidated. Here we show that
                      pEAβ(3-42) forms fibrils much faster than Aβ(1-42) and the
                      critical concentration above which aggregation was observed
                      was drastically decreased by one order of magnitude compared
                      to Aβ(1-42). We elucidated the co-aggregation mechanism of
                      Aβ(1-42) with pEAβ(3-42). At concentrations at which both
                      species do not aggregate as homofibrils, mixtures of
                      pEAβ(3-42) and Aβ(1-42) aggregate, suggesting the
                      formation of mixed nuclei. We show that the presence of
                      pEAβ(3-42) monomers increases the rate of primary
                      nucleation of Aβ(1-42) and that fibrils of pEAβ(3-42)
                      serve as highly efficient templates for elongation and
                      catalytic surfaces for secondary nucleation of Aβ(1-42). On
                      the other hand, the addition of Aβ(1-42) monomers
                      drastically decelerates the primary and secondary nucleation
                      of pEAβ(3-42) while not altering the pEAβ(3-42) elongation
                      rate. In addition, even moderate concentrations of fibrillar
                      Aβ(1-42) prevent pEAβ(3-42) aggregation, likely due to
                      non-reactive binding of pEAβ(3-42) monomers to the surfaces
                      of Aβ(1-42) fibrils. Thus, pEAβ(3-42) accelerates
                      aggregation of Aβ(1-42) by affecting all individual
                      reaction steps of the aggregation process while Aβ(1-42)
                      dramatically slows down the primary and secondary nucleation
                      of pEAβ(3-42).},
      cin          = {ICS-6},
      ddc          = {540},
      cid          = {I:(DE-Juel1)ICS-6-20110106},
      pnm          = {553 - Physical Basis of Diseases (POF3-553)},
      pid          = {G:(DE-HGF)POF3-553},
      typ          = {PUB:(DE-HGF)16},
      UT           = {WOS:000404617300034},
      doi          = {10.1039/C6SC04797A},
      url          = {https://juser.fz-juelich.de/record/836944},
}