論文 - 詳細
| RRC ID | 82828 |
|---|---|
| 著者 | Rajani RM, Ellingford R, Hellmuth M, Harris SS, Taso OS, Graykowski D, Lam FKW, Arber C, Fertan E, Danial JSH, Swire M, Lloyd M, Giovannucci TA, Bourdenx M, Klenerman D, Vassar R, Wray S, Sala Frigerio C, Busche MA. |
| タイトル | Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease. |
| ジャーナル | PLoS Biol |
| 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. |
| 巻・号 | 22(7) |
| ページ | e3002727 |
| 公開日 | 2024-7-1 |
| DOI | 10.1371/journal.pbio.3002727 |
| PII | PBIOLOGY-D-24-01895 |
| PMID | 39042667 |
| PMC | PMC11265669 |
| MeSH | Alzheimer Disease* / genetics Alzheimer Disease* / metabolism Alzheimer Disease* / pathology Amyloid beta-Peptides* / metabolism Animals Brain / metabolism Brain / pathology Disease Models, Animal* Female Gene Knock-In Techniques Humans Male Mice Mice, Transgenic* Neurons* / metabolism Oligodendroglia* / metabolism |
| IF | 7.076 |
| リソース情報 | |
| 実験動物マウス | RBRC06344 |