TY  - JOUR
AU  - Nussbaum, Justin M
AU  - Schilling, Stephan
AU  - Cynis, Holger
AU  - Silva, Antonia
AU  - Swanson, Eric
AU  - Wangsanut, Tanaporn
AU  - Tayler, Kaycie
AU  - Wiltgen, Brian
AU  - Hatami, Asa
AU  - Rönicke, Raik
AU  - Reymann, Klaus
AU  - Hutter-Paier, Birgit
AU  - Alexandru, Anca
AU  - Jagla, Wolfgang
AU  - Graubner, Sigrid
AU  - Glabe, Charles G
AU  - Demuth, Hans-Ulrich
AU  - Bloom, George S
TI  - Prion-like behaviour and tau-dependent cytotoxicity of pyroglutamylated amyloid-β.
JO  - Nature 
VL  - 485
IS  - 7400
SN  - 0028-0836
CY  - London [u.a.]
PB  - Nature Publ. Group65848
M1  - DZNE-2020-02851
SP  - 651-655
PY  - 2012
AB  - 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
KW  - Alzheimer Disease: metabolism
KW  - Amyloid: chemistry
KW  - Amyloid: drug effects
KW  - Amyloid: metabolism
KW  - Amyloid: toxicity
KW  - Amyloid beta-Peptides: chemistry
KW  - Amyloid beta-Peptides: genetics
KW  - Amyloid beta-Peptides: metabolism
KW  - Amyloid beta-Peptides: toxicity
KW  - Animals
KW  - Disease Models, Animal
KW  - Glutamic Acid: chemistry
KW  - Glutamic Acid: metabolism
KW  - Humans
KW  - Mice
KW  - Mice, Transgenic
KW  - Mutant Proteins: chemistry
KW  - Mutant Proteins: genetics
KW  - Mutant Proteins: metabolism
KW  - Mutant Proteins: toxicity
KW  - Peptide Fragments: chemistry
KW  - Peptide Fragments: genetics
KW  - Peptide Fragments: metabolism
KW  - Peptide Fragments: toxicity
KW  - Prions: chemistry
KW  - Prions: metabolism
KW  - Prions: toxicity
KW  - tau Proteins: deficiency
KW  - tau Proteins: genetics
KW  - tau Proteins: metabolism
KW  - Amyloid (NLM Chemicals)
KW  - Amyloid beta-Peptides (NLM Chemicals)
KW  - Mutant Proteins (NLM Chemicals)
KW  - Peptide Fragments (NLM Chemicals)
KW  - Prions (NLM Chemicals)
KW  - amyloid beta-protein (1-42) (NLM Chemicals)
KW  - tau Proteins (NLM Chemicals)
KW  - Glutamic Acid (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:22660329
C2  - pmc:PMC3367389
DO  - DOI:10.1038/nature11060
UR  - https://pub.dzne.de/record/136529
ER  -