Journal Article

DZNE-2024-01102

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer's disease model mice.

Sasmita, A. O. ; Depp, C. ; Nazarenko, T.Extern* ; Sun, T. ; Siems, S. B. ; Ong, E. C. ; Nkeh, Y. B. ; Böhler, C. ; Yu, X. ; Bues, B. ; Evangelista, L. ; Mao, S. ; Morgado, B. ; Wu, Z. ; Ruhwedel, T. ; Subramanian, S. ; Börensen, F. ; Overhoff, K. ; Spieth, L.Extern* ; Berghoff, S.Extern* ; Sadleir, K. R. ; Vassar, R. ; Eggert, S. ; Goebbels, S. ; Saito, T. ; Saido, T. ; Saher, G. ; Möbius, W. ; Castelo-Branco, G. ; Klafki, H.-W. ; Wirths, O. ; Wiltfang, J.DZNE* ; Jäkel, S. ; Yan, R. ; Nave, K.-A.

2024
Nature America New York, NY

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Please use a persistent id in citations: doi:10.1038/s41593-024-01730-3

Abstract: Amyloid-β (Aβ) is thought to be neuronally derived in Alzheimer's disease (AD). However, transcripts of amyloid precursor protein (APP) and amyloidogenic enzymes are equally abundant in oligodendrocytes (OLs). By cell-type-specific deletion of Bace1 in a humanized knock-in AD model, APPNLGF, we demonstrate that OLs and neurons contribute to Aβ plaque burden. For rapid plaque seeding, excitatory projection neurons must provide a threshold level of Aβ. Ultimately, our findings are relevant for AD prevention and therapeutic strategies.

Keyword(s): Animals (MeSH) ; Alzheimer Disease: metabolism (MeSH) ; Alzheimer Disease: pathology (MeSH) ; Alzheimer Disease: genetics (MeSH) ; Neurons: metabolism (MeSH) ; Neurons: pathology (MeSH) ; Oligodendroglia: metabolism (MeSH) ; Oligodendroglia: pathology (MeSH) ; Amyloid beta-Peptides: metabolism (MeSH) ; Disease Models, Animal (MeSH) ; Plaque, Amyloid: pathology (MeSH) ; Plaque, Amyloid: metabolism (MeSH) ; Amyloid Precursor Protein Secretases: metabolism (MeSH) ; Mice (MeSH) ; Mice, Transgenic (MeSH) ; Aspartic Acid Endopeptidases: metabolism (MeSH) ; Humans (MeSH) ; Amyloid beta-Protein Precursor: metabolism (MeSH) ; Amyloid beta-Protein Precursor: genetics (MeSH) ; Amyloid beta-Peptides ; Amyloid Precursor Protein Secretases ; Aspartic Acid Endopeptidases ; Amyloid beta-Protein Precursor ; Bace1 protein, mouse

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Contributing Institute(s):

1. Molecular biomarkers for predictive diagnostics of neurodegenerative diseases (AG Wiltfang)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2024

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Database coverage:
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