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GEO help: Mouse over screen elements for information. |
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| Status |
Public on Jan 06, 2023 |
| Title |
Neuronal APOE4 removal strongly protects against Tau-mediated gliosis, neurodegeneration, and myelin deficits |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Apolipoprotein E4 (APOE4) is the strongest known genetic risk factor for late-onset Alzheimer’s disease (AD). Conditions of stress or injury induce APOE expression within neurons, but the exact roles of neuronal APOE4 in AD pathogenesis are still unclear. Here we report a rigorous characterization of neuronal APOE4 effects on prominent AD-related pathologies by selectively removing APOE4 from neurons in an APOE4-expressing tauopathy mouse model. We found that the removal of neuronal APOE4 led to a drastic reduction in Tau pathology accumulation and spread, gliosis, neurodegeneration, neurodysfunction, and myelin deficits in this tauopathy mouse model. Single-nucleus RNA-sequencing revealed that the removal of neuronal APOE4 greatly diminished neurodegenerative disease-associated subpopulations of neurons, oligodendrocytes, astrocytes, and microglia that were enriched in APOE4-expressing tauopathy mice and whose accumulation correlated to the severity of Tau pathology, neurodegeneration, and myelin deficits. Thus, neuronal APOE4 plays a central role in promoting the development of major AD pathologies and its removal can effectively combat APOE4-driven effects in AD and other tauopathies.
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| Overall design |
Single-nucleus RNA sequencing on isolated hippocampi from 10-month-old PS19-fE4 mice with or without Syn1-Cre and PS19-fE3 mice.
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| Contributor(s) |
Koutsodendris N, Blumenfeld J, Agrawal A, Traglia M, Grone B, Thomas R, Huang Y |
| Citation(s) |
37118426 |
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| Submission date |
Dec 17, 2022 |
| Last update date |
Aug 02, 2023 |
| Contact name |
Ayushi Agrawal |
| E-mail(s) |
ayushi.agrawal@gladstone.ucsf.edu
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| Organization name |
Gladstone Institutes
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| Street address |
1650 Owens St
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94158 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA913415 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE221215_RAW.tar |
230.2 Mb |
(http)(custom) |
TAR (of H5) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
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