% 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{Nussbaum:136529,
      author       = {Nussbaum, Justin M and Schilling, Stephan and Cynis, Holger
                      and Silva, Antonia and Swanson, Eric and Wangsanut, Tanaporn
                      and Tayler, Kaycie and Wiltgen, Brian and Hatami, Asa and
                      Rönicke, Raik and Reymann, Klaus and Hutter-Paier, Birgit
                      and Alexandru, Anca and Jagla, Wolfgang and Graubner, Sigrid
                      and Glabe, Charles G and Demuth, Hans-Ulrich and Bloom,
                      George S},
      title        = {{P}rion-like behaviour and tau-dependent cytotoxicity of
                      pyroglutamylated amyloid-β.},
      journal      = {Nature},
      volume       = {485},
      number       = {7400},
      issn         = {0028-0836},
      address      = {London [u.a.]},
      publisher    = {Nature Publ. Group65848},
      reportid     = {DZNE-2020-02851},
      pages        = {651-655},
      year         = {2012},
      abstract     = {Extracellular plaques of amyloid-β and intraneuronal
                      neurofibrillary tangles made from tau are the
                      histopathological signatures of Alzheimer's disease. Plaques
                      comprise amyloid-β fibrils that assemble from monomeric and
                      oligomeric intermediates, and are prognostic indicators of
                      Alzheimer's disease. Despite the importance of plaques to
                      Alzheimer's disease, oligomers are considered to be the
                      principal toxic forms of amyloid-β. Interestingly, many
                      adverse responses to amyloid-β, such as cytotoxicity,
                      microtubule loss, impaired memory and learning, and neuritic
                      degeneration, are greatly amplified by tau expression.
                      Amino-terminally truncated, pyroglutamylated (pE) forms of
                      amyloid-β are strongly associated with Alzheimer's disease,
                      are more toxic than amyloid-β, residues 1-42 (Aβ(1-42))
                      and Aβ(1-40), and have been proposed as initiators of
                      Alzheimer's disease pathogenesis. Here we report a mechanism
                      by which pE-Aβ may trigger Alzheimer's disease.
                      Aβ(3(pE)-42) co-oligomerizes with excess Aβ(1-42) to form
                      metastable low-n oligomers (LNOs) that are structurally
                      distinct and far more cytotoxic to cultured neurons than
                      comparable LNOs made from Aβ(1-42) alone. Tau is required
                      for cytotoxicity, and LNOs comprising $5\%$ Aβ(3(pE)-42)
                      plus $95\%$ Aβ(1-42) $(5\%$ pE-Aβ) seed new cytotoxic LNOs
                      through multiple serial dilutions into Aβ(1-42) monomers in
                      the absence of additional Aβ(3(pE)-42). LNOs isolated from
                      human Alzheimer's disease brain contained Aβ(3(pE)-42), and
                      enhanced Aβ(3(pE)-42) formation in mice triggered neuron
                      loss and gliosis at 3 months, but not in a tau-null
                      background. We conclude that Aβ(3(pE)-42) confers
                      tau-dependent neuronal death and causes template-induced
                      misfolding of Aβ(1-42) into structurally distinct LNOs that
                      propagate by a prion-like mechanism. Our results raise the
                      possibility that Aβ(3(pE)-42) acts similarly at a primary
                      step in Alzheimer's disease pathogenesis.},
      keywords     = {Alzheimer Disease: metabolism / Amyloid: chemistry /
                      Amyloid: drug effects / Amyloid: metabolism / Amyloid:
                      toxicity / Amyloid beta-Peptides: chemistry / Amyloid
                      beta-Peptides: genetics / Amyloid beta-Peptides: metabolism
                      / Amyloid beta-Peptides: toxicity / Animals / Disease
                      Models, Animal / Glutamic Acid: chemistry / Glutamic Acid:
                      metabolism / Humans / Mice / Mice, Transgenic / Mutant
                      Proteins: chemistry / Mutant Proteins: genetics / Mutant
                      Proteins: metabolism / Mutant Proteins: toxicity / Peptide
                      Fragments: chemistry / Peptide Fragments: genetics / Peptide
                      Fragments: metabolism / Peptide Fragments: toxicity /
                      Prions: chemistry / Prions: metabolism / Prions: toxicity /
                      tau Proteins: deficiency / tau Proteins: genetics / tau
                      Proteins: metabolism / Amyloid (NLM Chemicals) / Amyloid
                      beta-Peptides (NLM Chemicals) / Mutant Proteins (NLM
                      Chemicals) / Peptide Fragments (NLM Chemicals) / Prions (NLM
                      Chemicals) / amyloid beta-protein (1-42) (NLM Chemicals) /
                      tau Proteins (NLM Chemicals) / Glutamic Acid (NLM
                      Chemicals)},
      cin          = {AG Reymann},
      ddc          = {500},
      cid          = {I:(DE-2719)1310005},
      pnm          = {342 - Disease Mechanisms and Model Systems (POF3-342)},
      pid          = {G:(DE-HGF)POF3-342},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:22660329},
      pmc          = {pmc:PMC3367389},
      doi          = {10.1038/nature11060},
      url          = {https://pub.dzne.de/record/136529},
}