eprintid: 10200946 rev_number: 8 eprint_status: archive userid: 699 dir: disk0/10/20/09/46 datestamp: 2024-12-03 11:20:09 lastmod: 2024-12-03 11:20:09 status_changed: 2024-12-03 11:20:09 type: article metadata_visibility: show sword_depositor: 699 creators_name: Rajani, Rikesh M creators_name: Ellingford, Robert creators_name: Hellmuth, Mariam creators_name: Harris, Samuel S creators_name: Taso, Orjona S creators_name: Graykowski, David creators_name: Lam, Francesca Kar Wey creators_name: Arber, Charles creators_name: Fertan, Emre creators_name: Danial, John SH creators_name: Swire, Matthew creators_name: Lloyd, Marcus creators_name: Giovannucci, Tatiana A creators_name: Bourdenx, Mathieu creators_name: Klenerman, David creators_name: Vassar, Robert creators_name: Wray, Selina creators_name: Sala Frigerio, Carlo creators_name: Busche, Marc Aurel title: Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease ispublished: pub divisions: UCL divisions: B02 divisions: C07 divisions: C10 divisions: D07 divisions: D17 divisions: F86 divisions: FD9 divisions: G95 keywords: Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Biology, Life Sciences & Biomedicine - Other Topics, PLURIPOTENT STEM-CELLS, MOUSE MODEL, CORTEX, TRANSCRIPTOMICS, MYELINATION, INHIBITION, ASTROCYTES, PATHOLOGY, PLAQUES note: Copyright: © 2024 Rajani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. abstract: Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer’s disease (AD), but the underlying assumption that neurons are the main source of pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of Aβ in the human brain and play a key role in promoting abnormal neuronal hyperactivity in an AD knock-in mouse model. We show that selectively suppressing oligodendrocyte Aβ production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte Aβ production could be a promising therapeutic strategy for treating AD. date: 2024-07 date_type: published publisher: PUBLIC LIBRARY SCIENCE official_url: http://dx.doi.org/10.1371/journal.pbio.3002727 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Article; Journal verified: verified_manual elements_id: 2299342 doi: 10.1371/journal.pbio.3002727 medium: Electronic-eCollection pii: PBIOLOGY-D-24-01895 lyricists_name: Rajani, Rikesh lyricists_name: Busche, Marc lyricists_name: Bourdenx, Mathieu lyricists_name: Wray, Selina lyricists_name: Ellingford, Robert lyricists_name: Swire, Matthew lyricists_name: Arber, Charles lyricists_name: Alvarez Giovannucci, Tatiana lyricists_id: RRAJA32 lyricists_id: MABUS87 lyricists_id: MBOUR65 lyricists_id: SWRAY93 lyricists_id: RELLI12 lyricists_id: MSWIR58 lyricists_id: CARBE72 lyricists_id: TALVA51 actors_name: Alvarez Giovannucci, Tatiana actors_id: TALVA51 actors_role: owner funding_acknowledgements: [UK Dementia Research Institute through UK DRI Ltd]; [UK Medical Research Council]; MR/X011038/1 [UKRI Future Leaders Fellowship]; NC/W001675/1 [NC3Rs studentship grant]; AARF-23-1149637 [Alzheimer's Association International Research Fellowship]; [National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre]; MR/X019977/1 [MRC Career Development Award]; 23AARFD-1029918 [Alzheimer's Association Research Fellowship] full_text_status: public publication: PLoS Biology volume: 22 number: 7 article_number: ARTN e3002727 pages: 30 event_location: United States issn: 1544-9173 editors_name: Simons, Mikael citation: Rajani, Rikesh M; Ellingford, Robert; Hellmuth, Mariam; Harris, Samuel S; Taso, Orjona S; Graykowski, David; Lam, Francesca Kar Wey; ... Busche, Marc Aurel; + view all <#> Rajani, Rikesh M; Ellingford, Robert; Hellmuth, Mariam; Harris, Samuel S; Taso, Orjona S; Graykowski, David; Lam, Francesca Kar Wey; Arber, Charles; Fertan, Emre; Danial, John SH; Swire, Matthew; Lloyd, Marcus; Giovannucci, Tatiana A; Bourdenx, Mathieu; Klenerman, David; Vassar, Robert; Wray, Selina; Sala Frigerio, Carlo; Busche, Marc Aurel; - view fewer <#> (2024) Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease. PLoS Biology , 22 (7) , Article ARTN e3002727. 10.1371/journal.pbio.3002727 <https://doi.org/10.1371/journal.pbio.3002727>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10200946/1/Selective%20suppression%20of%20oligodendrocyte-derived%20amyloid%20beta%20rescues%20neuronal%20dysfunction%20in%20Alzheimers%20disease.pdf