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

• DOI: 10.1371/journal.pbio.3002727
• Publication Date: 2024-07-23T18:54:44Z
• Authors: Rikesh M. Rajani; Robert Ellingford; Mariam Hellmuth; Samuel S. Harris; Orjona S. Taso; David Graykowski; Francesca Kar Wey...; Charles Arber; Emre Fertan; John S. H. Danial; Matthew Swire; Marcus Lloyd; Tatiana A. Giovan...; Mathieu Bourdenx; David Klenerman; Robert Vassar; Selina Wray; Carlo Sala Frigerio; Marc Aurel Busche
• Keywords: Amyloid beta; BETA (programming language); Amyloid (mycology)

Reduction of amyloid beta (Aβ) has been shown to be effective in treating Alzheimer's disease (AD), but the underlying assumption that neurons are main source pathogenic Aβ is untested. Here, we challenge this prevailing belief by demonstrating oligodendrocytes an important human brain and play a key role promoting abnormal neuronal hyperactivity AD knock-in mouse model. We show selectively suppressing oligodendrocyte production improves pathology restores function model vivo. Our findings suggest targeting could promising therapeutic strategy for AD.