Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer’s disease
Year: 2024
Type: article
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.
Source: PLoS Biology
Authors: 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
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,500
Funders: Alzheimer's Association, UK Research and Innovation, National Institute for Health and Care Research, University College London, National Centre for the Replacement, Refinement and Reduction of Animals in Research, Westfälische Wilhelms-Universität Münster, UK Dementia Research Institute, Medical Research Council, Reta Lila Weston Institute of Neurological Studies, UCL Queen Square Institute of Neurology,University College London
Awards: Influence of the Microenvironment on the Turnover of Fluid Biomarkers, Cellular and circuit mechanisms of Alzheimer's disease, Elucidating the Proteinopathic Drivers of Network Dysfunction in AD, How does Adaptive Myelination Re-shape Neural Circuits During Learning?, G6871624426, G8252173002
OpenAlex ID: W4400906342