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bioRxiv · 10.1101/2024.06.21.600003

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

Rajani, R.·Ellingford, R.·Hellmuth, M.·Harris, S.·Taso, O.·Graykowski, D.·Lam, F.·Arber, C.·Fertan, E.·Danial, J. S. H.·Swire, M.·Lloyd, M.·Giovannucci, T.·Bourdenx, M.·Klenerman, D.·Vassar, R.·Wray, S.·Sala-Frigerio, C.·Busche, M. A.
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Abstract

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

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Rajani, R., Ellingford, R., Hellmuth, M., Harris, S., Taso, O., Graykowski, D., Lam, F., Arber, C., Fertan, E., Danial, J. S. H., Swire, M., Lloyd, M., Giovannucci, T., Bourdenx, M., Klenerman, D., Vassar, R., Wray, S., Sala-Frigerio, C., Busche, M. A.. 2024-06-27. Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's Disease. https://doi.org/10.1101/2024.06.21.600003

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