%0 Journal Article
%A Nussbaum, Justin M
%A Schilling, Stephan
%A Cynis, Holger
%A Silva, Antonia
%A Swanson, Eric
%A Wangsanut, Tanaporn
%A Tayler, Kaycie
%A Wiltgen, Brian
%A Hatami, Asa
%A Rönicke, Raik
%A Reymann, Klaus
%A Hutter-Paier, Birgit
%A Alexandru, Anca
%A Jagla, Wolfgang
%A Graubner, Sigrid
%A Glabe, Charles G
%A Demuth, Hans-Ulrich
%A Bloom, George S
%T Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β.
%J Nature 
%V 485
%N 7400
%@ 0028-0836
%C London [u.a.]
%I Nature Publ. Group65848
%M DZNE-2020-02851
%P 651-655
%D 2012
%X 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
%K Alzheimer Disease: metabolism
%K Amyloid: chemistry
%K Amyloid: drug effects
%K Amyloid: metabolism
%K Amyloid: toxicity
%K Amyloid beta-Peptides: chemistry
%K Amyloid beta-Peptides: genetics
%K Amyloid beta-Peptides: metabolism
%K Amyloid beta-Peptides: toxicity
%K Animals
%K Disease Models, Animal
%K Glutamic Acid: chemistry
%K Glutamic Acid: metabolism
%K Humans
%K Mice
%K Mice, Transgenic
%K Mutant Proteins: chemistry
%K Mutant Proteins: genetics
%K Mutant Proteins: metabolism
%K Mutant Proteins: toxicity
%K Peptide Fragments: chemistry
%K Peptide Fragments: genetics
%K Peptide Fragments: metabolism
%K Peptide Fragments: toxicity
%K Prions: chemistry
%K Prions: metabolism
%K Prions: toxicity
%K tau Proteins: deficiency
%K tau Proteins: genetics
%K tau Proteins: metabolism
%K Amyloid (NLM Chemicals)
%K Amyloid beta-Peptides (NLM Chemicals)
%K Mutant Proteins (NLM Chemicals)
%K Peptide Fragments (NLM Chemicals)
%K Prions (NLM Chemicals)
%K amyloid beta-protein (1-42) (NLM Chemicals)
%K tau Proteins (NLM Chemicals)
%K Glutamic Acid (NLM Chemicals)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:22660329
%2 pmc:PMC3367389
%R 10.1038/nature11060
%U https://pub.dzne.de/record/136529