Oligodendrocytes produce amyloid-β and contribute to plaque formation alongside neurons in Alzheimer’s disease model mice
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<sup>NLGF</sup>, 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.
Authors
- Jens Wiltfang (ORCID: https://orcid.org/0000-0003-1492-5330)
- Takashi Saito (ORCID: https://orcid.org/0000-0002-9659-9251)
- Constanze Depp (ORCID: https://orcid.org/0000-0003-2868-6932)
- Swati Subramanian
- Takaomi C. Saido (ORCID: https://orcid.org/0000-0003-1970-6903)
- Robert Vassar (ORCID: https://orcid.org/0000-0002-1358-504X)
- Sophie B. Siems (ORCID: https://orcid.org/0000-0002-7760-2507)
- Xuan Yu (ORCID: https://orcid.org/0000-0001-6826-7260)
- Simone Eggert (ORCID: https://orcid.org/0000-0002-6792-5556)
- Bastian Bues (ORCID: https://orcid.org/0000-0002-8302-6235)
- Riqiang Yan (ORCID: https://orcid.org/0000-0001-7195-7617)
- Klaus‐Armin Nave (ORCID: https://orcid.org/0000-0001-8724-9666)
- Torben Ruhwedel (ORCID: https://orcid.org/0000-0002-9535-9395)
- Gonçalo Castelo‐Branco (ORCID: https://orcid.org/0000-0003-2247-9393)
- Katherine R. Sadleir
- Andrew Octavian Sasmita (ORCID: https://orcid.org/0000-0001-7379-6749)
- Lena Spieth (ORCID: https://orcid.org/0000-0002-0308-0144)
- Hans‐Wolfgang Klafki (ORCID: https://orcid.org/0000-0002-8672-9032)
- Oliver Wirths (ORCID: https://orcid.org/0000-0002-4115-0334)
- Stefan A. Berghoff (ORCID: https://orcid.org/0000-0002-3794-7295)
- Ting Sun (ORCID: https://orcid.org/0000-0002-7104-7215)
- Gesine Saher (ORCID: https://orcid.org/0000-0003-3507-9604)
- Shuying Mao
- Bárbara Morgado (ORCID: https://orcid.org/0000-0001-8174-9301)
- Sandra Goebbels (ORCID: https://orcid.org/0000-0001-8343-9972)
- Carolin Böhler
- Katharina Overhoff
- Friederike Börensen
- Yakum Bertrand Nkeh (ORCID: https://orcid.org/0009-0006-9601-4408)
- Sarah Jäkel (ORCID: https://orcid.org/0000-0002-9634-2472)
- T. I. Nazarenko
- Erinne Cherisse Ong
- Zoe Y. Wu
- Lisa Evangelista
- Wiebke Möbius (ORCID: https://orcid.org/0000-0002-2902-7165)
Institutions
- Northwestern University (US)
- University College Cork (IE)
- RIKEN Center for Brain Science (JP)
- German Center for Neurodegenerative Diseases (DE)
- Karolinska Institutet (SE)
- Max Planck Institute for the Study of Religious and Ethnic Diversity (DE)
- Munich Cluster for Systems Neurology (DE)
- Max Planck Institute for Solar System Research (DE)
- Max Planck Institute of Experimental Medicine (DE)
- Max Planck Institute for Multidisciplinary Sciences (DE)
- University of Göttingen (DE)
- UConn Health (US)
- Ludwig-Maximilians-Universität München (DE)
Publication Details
- Journal
- Nature Neuroscience
- Published
- 2024-08-05
- DOI
- https://doi.org/10.1038/s41593-024-01730-3
- Citations
- 90
- Primary Topic
- Alzheimer's disease research and treatments
- Type
- article
- Field-Weighted Citation Impact
- 29.39
Funders
- Deutsche Forschungsgemeinschaft
- Max-Planck-Gesellschaft