Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease.

Autor: Rikesh M Rajani, Robert Ellingford, Mariam Hellmuth, Samuel S Harris, Orjona S Taso, David Graykowski, Francesca Kar Wey Lam, Charles Arber, Emre Fertan, John S H Danial, Matthew Swire, Marcus Lloyd, Tatiana A Giovannucci, Mathieu Bourdenx, David Klenerman, Robert Vassar, Selina Wray, Carlo Sala Frigerio, Marc Aurel Busche
Jazyk: angličtina
Rok vydání: 2024
Předmět:
Zdroj: PLoS Biology, Vol 22, Iss 7, p e3002727 (2024)
Druh dokumentu: article
ISSN: 1544-9173
1545-7885
DOI: 10.1371/journal.pbio.3002727&type=printable
Popis: 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.
Databáze: Directory of Open Access Journals
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje