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| 001 | 136529 | ||
| 005 | 20240321220103.0 | ||
| 024 | 7 | _ | |a 10.1038/nature11060 |2 doi |
| 024 | 7 | _ | |a pmid:22660329 |2 pmid |
| 024 | 7 | _ | |a pmc:PMC3367389 |2 pmc |
| 024 | 7 | _ | |a 0028-0836 |2 ISSN |
| 024 | 7 | _ | |a 1476-4687 |2 ISSN |
| 024 | 7 | _ | |a altmetric:722329 |2 altmetric |
| 037 | _ | _ | |a DZNE-2020-02851 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 500 |
| 100 | 1 | _ | |a Nussbaum, Justin M |0 P:(DE-HGF)0 |b 0 |
| 245 | _ | _ | |a Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β. |
| 260 | _ | _ | |a London [u.a.] |c 2012 |b Nature Publ. Group65848 |
| 264 | _ | 1 | |3 online |2 Crossref |b Springer Science and Business Media LLC |c 2012-05-02 |
| 264 | _ | 1 | |3 print |2 Crossref |b Springer Science and Business Media LLC |c 2012-05-01 |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1585319198_16440 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 520 | _ | _ | |a 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. |
| 536 | _ | _ | |a 342 - Disease Mechanisms and Model Systems (POF3-342) |0 G:(DE-HGF)POF3-342 |c POF3-342 |f POF III |x 0 |
| 542 | _ | _ | |i 2012-05-01 |2 Crossref |u http://www.springer.com/tdm |
| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, |
| 650 | _ | 7 | |a Amyloid |2 NLM Chemicals |
| 650 | _ | 7 | |a Amyloid beta-Peptides |2 NLM Chemicals |
| 650 | _ | 7 | |a Mutant Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Peptide Fragments |2 NLM Chemicals |
| 650 | _ | 7 | |a Prions |2 NLM Chemicals |
| 650 | _ | 7 | |a amyloid beta-protein (1-42) |2 NLM Chemicals |
| 650 | _ | 7 | |a tau Proteins |2 NLM Chemicals |
| 650 | _ | 7 | |a Glutamic Acid |0 3KX376GY7L |2 NLM Chemicals |
| 650 | _ | 2 | |a Alzheimer Disease: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid: chemistry |2 MeSH |
| 650 | _ | 2 | |a Amyloid: drug effects |2 MeSH |
| 650 | _ | 2 | |a Amyloid: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid: toxicity |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: chemistry |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: genetics |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: metabolism |2 MeSH |
| 650 | _ | 2 | |a Amyloid beta-Peptides: toxicity |2 MeSH |
| 650 | _ | 2 | |a Animals |2 MeSH |
| 650 | _ | 2 | |a Disease Models, Animal |2 MeSH |
| 650 | _ | 2 | |a Glutamic Acid: chemistry |2 MeSH |
| 650 | _ | 2 | |a Glutamic Acid: metabolism |2 MeSH |
| 650 | _ | 2 | |a Humans |2 MeSH |
| 650 | _ | 2 | |a Mice |2 MeSH |
| 650 | _ | 2 | |a Mice, Transgenic |2 MeSH |
| 650 | _ | 2 | |a Mutant Proteins: chemistry |2 MeSH |
| 650 | _ | 2 | |a Mutant Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a Mutant Proteins: metabolism |2 MeSH |
| 650 | _ | 2 | |a Mutant Proteins: toxicity |2 MeSH |
| 650 | _ | 2 | |a Peptide Fragments: chemistry |2 MeSH |
| 650 | _ | 2 | |a Peptide Fragments: genetics |2 MeSH |
| 650 | _ | 2 | |a Peptide Fragments: metabolism |2 MeSH |
| 650 | _ | 2 | |a Peptide Fragments: toxicity |2 MeSH |
| 650 | _ | 2 | |a Prions: chemistry |2 MeSH |
| 650 | _ | 2 | |a Prions: metabolism |2 MeSH |
| 650 | _ | 2 | |a Prions: toxicity |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: deficiency |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: genetics |2 MeSH |
| 650 | _ | 2 | |a tau Proteins: metabolism |2 MeSH |
| 700 | 1 | _ | |a Schilling, Stephan |0 P:(DE-HGF)0 |b 1 |
| 700 | 1 | _ | |a Cynis, Holger |0 P:(DE-HGF)0 |b 2 |
| 700 | 1 | _ | |a Silva, Antonia |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Swanson, Eric |0 P:(DE-HGF)0 |b 4 |
| 700 | 1 | _ | |a Wangsanut, Tanaporn |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Tayler, Kaycie |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Wiltgen, Brian |0 P:(DE-HGF)0 |b 7 |
| 700 | 1 | _ | |a Hatami, Asa |0 P:(DE-HGF)0 |b 8 |
| 700 | 1 | _ | |a Rönicke, Raik |0 P:(DE-2719)2321269 |b 9 |u dzne |
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| 700 | 1 | _ | |a Hutter-Paier, Birgit |0 P:(DE-HGF)0 |b 11 |
| 700 | 1 | _ | |a Alexandru, Anca |0 P:(DE-HGF)0 |b 12 |
| 700 | 1 | _ | |a Jagla, Wolfgang |0 P:(DE-HGF)0 |b 13 |
| 700 | 1 | _ | |a Graubner, Sigrid |0 P:(DE-HGF)0 |b 14 |
| 700 | 1 | _ | |a Glabe, Charles G |0 P:(DE-HGF)0 |b 15 |
| 700 | 1 | _ | |a Demuth, Hans-Ulrich |0 P:(DE-HGF)0 |b 16 |
| 700 | 1 | _ | |a Bloom, George S |0 P:(DE-HGF)0 |b 17 |e Corresponding author |
| 773 | 1 | 8 | |a 10.1038/nature11060 |b : Springer Science and Business Media LLC, 2012-05-01 |n 7400 |p 651-655 |3 journal-article |2 Crossref |t Nature |v 485 |y 2012 |x 0028-0836 |
| 773 | _ | _ | |a 10.1038/nature11060 |g Vol. 485, no. 7400, p. 651 - 655 |0 PERI:(DE-600)1413423-8 |n 7400 |q 485:7400<651 - 655 |p 651-655 |t Nature |v 485 |y 2012 |x 0028-0836 |
| 856 | 7 | _ | |2 Pubmed Central |u http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3367389 |
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