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000154283 0247_ $$2doi$$a10.1038/s41593-020-00737-w
000154283 0247_ $$2pmid$$apmid:33199898
000154283 0247_ $$2pmc$$apmc:PMC7783656
000154283 0247_ $$2ISSN$$a1097-6256
000154283 0247_ $$2ISSN$$a1546-1726
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000154283 037__ $$aDZNE-2021-00137
000154283 041__ $$aEnglish
000154283 082__ $$a610
000154283 1001_ $$0P:(DE-2719)9001482$$aUhlmann, Ruth E$$b0$$eFirst author$$udzne
000154283 245__ $$aAcute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.
000154283 260__ $$aNew York, NY$$bNature America$$c2020
000154283 3367_ $$2DRIVER$$aarticle
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000154283 520__ $$aAmyloid-β (Aβ) deposits are a relatively late consequence of Aβ aggregation in Alzheimer's disease. When pathogenic Aβ seeds begin to form, propagate and spread is not known, nor are they biochemically defined. We tested various antibodies for their ability to neutralize Aβ seeds before Aβ deposition becomes detectable in Aβ precursor protein-transgenic mice. We also characterized the different antibody recognition profiles using immunoprecipitation of size-fractionated, native, mouse and human brain-derived Aβ assemblies. At least one antibody, aducanumab, after acute administration at the pre-amyloid stage, led to a significant reduction of Aβ deposition and downstream pathologies 6 months later. This demonstrates that therapeutically targetable pathogenic Aβ seeds already exist during the lag phase of protein aggregation in the brain. Thus, the preclinical phase of Alzheimer's disease-currently defined as Aβ deposition without clinical symptoms-may be a relatively late manifestation of a much earlier pathogenic seed formation and propagation that currently escapes detection in vivo.
000154283 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0
000154283 588__ $$aDataset connected to CrossRef, PubMed, , Journals: pub.dzne.de
000154283 650_7 $$2NLM Chemicals$$aAmyloid beta-Peptides
000154283 650_7 $$2NLM Chemicals$$aAmyloid beta-Protein Precursor
000154283 650_7 $$2NLM Chemicals$$aAntibodies, Blocking
000154283 650_7 $$2NLM Chemicals$$aAntibodies, Monoclonal, Humanized
000154283 650_7 $$2NLM Chemicals$$aNeurofilament Proteins
000154283 650_7 $$2NLM Chemicals$$aTissue Extracts
000154283 650_7 $$0105J35OE21$$2NLM Chemicals$$aaducanumab
000154283 650_2 $$2MeSH$$aAged
000154283 650_2 $$2MeSH$$aAged, 80 and over
000154283 650_2 $$2MeSH$$aAlzheimer Disease: metabolism
000154283 650_2 $$2MeSH$$aAlzheimer Disease: pathology
000154283 650_2 $$2MeSH$$aAmyloid beta-Peptides: metabolism
000154283 650_2 $$2MeSH$$aAmyloid beta-Protein Precursor: antagonists & inhibitors
000154283 650_2 $$2MeSH$$aAnimals
000154283 650_2 $$2MeSH$$aAntibodies, Blocking: pharmacology
000154283 650_2 $$2MeSH$$aAntibodies, Monoclonal, Humanized: pharmacokinetics
000154283 650_2 $$2MeSH$$aAntibodies, Monoclonal, Humanized: pharmacology
000154283 650_2 $$2MeSH$$aBrain Chemistry
000154283 650_2 $$2MeSH$$aHumans
000154283 650_2 $$2MeSH$$aMale
000154283 650_2 $$2MeSH$$aMice
000154283 650_2 $$2MeSH$$aMice, Inbred C57BL
000154283 650_2 $$2MeSH$$aMice, Transgenic
000154283 650_2 $$2MeSH$$aMiddle Aged
000154283 650_2 $$2MeSH$$aNeurofilament Proteins: cerebrospinal fluid
000154283 650_2 $$2MeSH$$aPlaque, Amyloid: pathology
000154283 650_2 $$2MeSH$$aTissue Extracts: pharmacology
000154283 7001_ $$0P:(DE-2719)9001483$$aRother, Christine$$b1$$udzne
000154283 7001_ $$0P:(DE-2719)2811173$$aRasmussen, Jay$$b2
000154283 7001_ $$0P:(DE-2719)2811018$$aSchelle, Juliane$$b3
000154283 7001_ $$0P:(DE-2719)9001484$$aBergmann, Carina$$b4$$udzne
000154283 7001_ $$0P:(DE-2719)9001485$$aUllrich Gavilanes, Emily M$$b5$$udzne
000154283 7001_ $$0P:(DE-2719)2451359$$aFritschi, Sarah$$b6
000154283 7001_ $$0P:(DE-2719)2813030$$aBuehler, Anika$$b7
000154283 7001_ $$0P:(DE-2719)9000018$$aBaumann, Frank$$b8
000154283 7001_ $$0P:(DE-2719)2810430$$aSkodras, Angelos$$b9
000154283 7001_ $$0P:(DE-2719)9001466$$aAl-Shaana, Rawaa$$b10$$udzne
000154283 7001_ $$0P:(DE-2719)9001120$$aBeschorner, Natalie$$b11
000154283 7001_ $$0P:(DE-2719)2811684$$aYe, Lan$$b12
000154283 7001_ $$0P:(DE-2719)9000387$$aKaeser, Stephan A$$b13
000154283 7001_ $$0P:(DE-2719)2814201$$aObermüller, Ulrike$$b14
000154283 7001_ $$aChristensen, Søren$$b15
000154283 7001_ $$aKartberg, Fredrik$$b16
000154283 7001_ $$aStavenhagen, Jeffrey B$$b17
000154283 7001_ $$aRahfeld, Jens-Ulrich$$b18
000154283 7001_ $$00000-0001-6655-7539$$aCynis, Holger$$b19
000154283 7001_ $$aQian, Fang$$b20
000154283 7001_ $$00000-0002-0802-0052$$aWeinreb, Paul H$$b21
000154283 7001_ $$00000-0002-6818-4876$$aBussiere, Thierry$$b22
000154283 7001_ $$0P:(DE-HGF)0$$aWalker, Lary C$$b23
000154283 7001_ $$0P:(DE-HGF)0$$aStaufenbiel, Matthias$$b24
000154283 7001_ $$0P:(DE-2719)2000010$$aJucker, Mathias$$b25$$eLast author
000154283 773__ $$0PERI:(DE-600)1494955-6$$a10.1038/s41593-020-00737-w$$gVol. 23, no. 12, p. 1580 - 1588$$n12$$p1580 - 1588$$tNature neuroscience$$v23$$x1546-1726$$y2020
000154283 8564_ $$uhttps://pubmed.ncbi.nlm.nih.gov/33199898/
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