TY  - JOUR
TI  - Selective suppression of oligodendrocyte-derived amyloid beta rescues neuronal dysfunction in Alzheimer's disease
AV  - public
Y1  - 2024/07//
EP  - 30
N2  - Reduction of amyloid beta (A?) has been shown to be effective in treating Alzheimer?s disease (AD), but the underlying assumption that neurons are the main source of pathogenic A? is untested. Here, we challenge this prevailing belief by demonstrating that oligodendrocytes are an important source of A? 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 A? production improves AD brain pathology and restores neuronal function in the mouse model in vivo. Our findings suggest that targeting oligodendrocyte A? production could be a promising therapeutic strategy for treating AD.
ID  - discovery10200946
PB  - PUBLIC LIBRARY SCIENCE
KW  - Science & Technology
KW  -  Life Sciences & Biomedicine
KW  -  Biochemistry & Molecular Biology
KW  -  Biology
KW  -  Life Sciences & Biomedicine - Other Topics
KW  -  PLURIPOTENT STEM-CELLS
KW  -  MOUSE MODEL
KW  -  CORTEX
KW  -  TRANSCRIPTOMICS
KW  -  MYELINATION
KW  -  INHIBITION
KW  -  ASTROCYTES
KW  -  PATHOLOGY
KW  -  PLAQUES
VL  - 22
IS  - 7
N1  - Copyright: © 2024 Rajani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
UR  - http://dx.doi.org/10.1371/journal.pbio.3002727
SN  - 1544-9173
JF  - PLoS Biology
A1  - Rajani, Rikesh M
A1  - Ellingford, Robert
A1  - Hellmuth, Mariam
A1  - Harris, Samuel S
A1  - Taso, Orjona S
A1  - Graykowski, David
A1  - Lam, Francesca Kar Wey
A1  - Arber, Charles
A1  - Fertan, Emre
A1  - Danial, John SH
A1  - Swire, Matthew
A1  - Lloyd, Marcus
A1  - Giovannucci, Tatiana A
A1  - Bourdenx, Mathieu
A1  - Klenerman, David
A1  - Vassar, Robert
A1  - Wray, Selina
A1  - Sala Frigerio, Carlo
A1  - Busche, Marc Aurel
ER  -