Journal Article

DZNE-2021-00137

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Acute targeting of pre-amyloid seeds in transgenic mice reduces Alzheimer-like pathology later in life.

Uhlmann, R. E. (First author)DZNE* ; Rother, C.DZNE* ; Rasmussen, J.DZNE* ; Schelle, J.DZNE* ; Bergmann, C.DZNE* ; Ullrich Gavilanes, E. M.DZNE* ; Fritschi, S.DZNE* ; Buehler, A.DZNE* ; Baumann, F.DZNE* ; Skodras, A.DZNE* ; Al-Shaana, R.DZNE* ; Beschorner, N.DZNE* ; Ye, L.DZNE* ; Kaeser, S. A.DZNE* ; Obermüller, U.DZNE* ; Christensen, S. ; Kartberg, F. ; Stavenhagen, J. B. ; Rahfeld, J.-U. ; Cynis, H. ; Qian, F. ; Weinreb, P. H. ; Bussiere, T. ; Walker, L. C. ; Staufenbiel, M. ; Jucker, M. (Last author)DZNE*

2020
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41593-020-00737-w

Abstract: Amyloid-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.

Keyword(s): Aged (MeSH) ; Aged, 80 and over (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Amyloid beta-Protein Precursor: antagonists & inhibitors (MeSH) ; Animals (MeSH) ; Antibodies, Blocking: pharmacology (MeSH) ; Antibodies, Monoclonal, Humanized: pharmacokinetics (MeSH) ; Antibodies, Monoclonal, Humanized: pharmacology (MeSH) ; Brain Chemistry (MeSH) ; Humans (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Inbred C57BL (MeSH) ; Mice, Transgenic (MeSH) ; Middle Aged (MeSH) ; Neurofilament Proteins: cerebrospinal fluid (MeSH) ; Plaque, Amyloid: pathology (MeSH) ; Tissue Extracts: pharmacology (MeSH) ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor ; Antibodies, Blocking ; Antibodies, Monoclonal, Humanized ; Neurofilament Proteins ; Tissue Extracts ; aducanumab

Note: ISSN 1546-1726 not unique: **3 hits**.

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Contributing Institute(s):

1. Cell Biology of Neurologic Diseases (AG Jucker)
2. Ext Universitätsklinikum Tübingen (Ext UKT)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)

Appears in the scientific report 2020

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 25 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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