Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice

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Abstract:

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,
                APP
                
                  NLGF
                
                , 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.

SEEK ID: https://goeseek.gwdguser.de/publications/34

DOI: 10.1038/s41593-024-01730-3

Projects: TRR 274: Checkpoints of Central Nervous System Recovery

Publication type: Journal Article

Journal: Nature Neuroscience

Book Title: Nature Neuroscience

Publisher: Springer Science and Business Media LLC

Citation: Nat Neurosci 27(9):1668-1674.

Date Published: 5th Aug 2024

Registered Mode: by DOI

Authors: Andrew Octavian Sasmita, Constanze Depp, Taisiia Nazarenko, Ting Sun, Sophie B. Siems, Erinne Cherisse Ong, Yakum B. Nkeh, Carolin Böhler, Xuan Yu, Bastian Bues, Lisa Evangelista, Shuying Mao, Barbara Morgado, Zoe Wu, Torben Ruhwedel, Swati Subramanian, Friederike Börensen, Katharina Overhoff, Lena Spieth, Stefan A. Berghoff, Katherine Rose Sadleir, Robert Vassar, Simone Eggert, Sandra Goebbels, Takashi Saito, Takaomi Saido, Gesine Saher, Wiebke Möbius, Gonçalo Castelo-Branco, Hans-Wolfgang Klafki, Oliver Wirths, Jens Wiltfang, Sarah Jäkel, Riqiang Yan, Klaus-Armin Nave

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Camilla Giudici

Citation

Sasmita, A. O., Depp, C., Nazarenko, T., 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., … Nave, K.-A. (2024). Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice. In Nature Neuroscience (Vol. 27, Issue 9, pp. 1668–1674). Springer Science and Business Media LLC. https://doi.org/10.1038/s41593-024-01730-3

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Created: 6th Aug 2026 at 13:48

Last updated: 6th Aug 2026 at 13:48

Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice

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