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| Status |
Public on Mar 20, 2023 |
| Title |
Transcriptome profiling of mouse brain microglia in Cnp null mice with 5xFAD background |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Alzheimer’s disease (AD) is the most common form of dementia and neurodegenerative disease with increasing prevalence due to longer lifespan in the human population. Why aging constitutes the greatest risk factor for development of AD, however, remains poorly understood. Aging markedly affects oligodendrocytes and the structural integrity of their myelin sheaths which also causes secondary tissue inflammation. We propose a mechanistic link between aging-associated myelin dysfunction and the deposition of Amyloid-ß (Aß) as primary neuropathological hallmark of early AD and hypothesized that breakdown of myelin - especially in cortical regions – is an upstream driver of amyloid deposition in AD. Here, we show that in transgenic mouse models of AD, genetically induced myelin defects by Cnp or Plp1 depletion, as well as direct demyelination are potent drivers of amyloid deposition in vivo as shown by light sheet microscopy imaging. At transcriptomic level, bulk and single-cell RNA sequencing revealed successfully induced disease-associated-microglia (DAM)-like phenotypes in Cnp-/- animals. These activated microglia, however, are primarily engaged with myelin seemingly preventing the protective reactions of the microglia pool to Aß plaques. Our work, therefore, identifies myelin aging as a previously overlooked risk factor for AD and makes the case for myelin health-directed therapies in AD.
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| Overall design |
Microglia cells from 6-month-old mouse brain hemispheres were isolated using the MACS sorting system and subjected to 50 bp single-end mRNA sequencing. Each genotype has n=4 replicates, in total 4 genotypes were included for experiment (WT, Cnp-/-, 5xFAD, Cnp-/-x5xFAD).
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| Contributor(s) |
Sun T, Depp C, Nave K |
| Citation(s) |
37258678 |
| Submission date |
Jun 16, 2021 |
| Last update date |
Jun 16, 2023 |
| Contact name |
Ting Sun |
| E-mail(s) |
tsun@mpinat.mpg.de
|
| Organization name |
Max Planck Institute for Multidisciplinary Sciencesi
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| Department |
Neurogenetics
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| Lab |
AG Nave
|
| Street address |
Hermann-Rein-Straße 3
|
| City |
Göttingen |
| State/province |
Germany (DEU) |
| ZIP/Postal code |
37075 |
| Country |
Germany |
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| Platforms (1) |
| GPL21103 |
Illumina HiSeq 4000 (Mus musculus) |
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| Samples (16)
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| This SubSeries is part of SuperSeries: |
| GSE178304 |
Ageing-associated myelin dysfunction drives amyloid deposition in mouse models of Alzheimer's disease |
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| Relations |
| BioProject |
PRJNA738380 |
| SRA |
SRP324250 |
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