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| Status |
Public on Feb 14, 2024 |
| Title |
Distinct transcriptomic responses to Ab plaques, neurofibrillary tangles, and APOE in Alzheimer’s disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
INTRODUCTION: Omics studies have revealed that various brain cell types undergo profound molecular changes in Alzheimer’s disease (AD) but the spatial relationships with plaques and tangles and APOE-linked differences remain unclear.
METHODS: We performed laser capture microdissection of Ab plaques, the 50mm halo around them, tangles with the 50mm halo around them, and areas distant (>50mm) from plaques and tangles in the temporal cortex of AD and control donors, followed by RNA-sequencing.
RESULTS: Ab plaques exhibited upregulated microglial (neuroinflammation) and downregulated neuronal (neurotransmission/energy metabolism) genes, whereas tangles had mostly downregulated neuronal genes. Ab plaques had more differentially expressed genes than tangles. We identified a gradient Ab plaque>peri-plaque>tangle>distant for these changes. AD APOEe4 homozygotes had greater changes than APOEe3 across locations, especially within Ab plaques.
DISCUSSION: Transcriptomic changes in AD consist primarily of neuroinflammation and neuronal dysfunction, are spatially associated mainly with Ab plaques, and are exacerbated by the APOEe4 allele.
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| Overall design |
Abeta plaques, the 50um halo around them, tangles with a 50um halo around them, and areas distant (>50um) from plaques and tangles in the temporal cortex of 10 Alzheimer's disease cases (n=5 APOEe4/e4, n=4 APOEe3/e3, and n=1 APOEe3/e4) were profiled, along with 8 age- and sex-matched control donors
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| Contributor(s) |
Das S, Li Z, Wachter A, Alla S, Noori A, Abdourahman A, Tamm JA, Woodbury ME, Talanian RV, Biber K, Karran EH, Hyman BT, Serrano-Pozo A |
| Citation(s) |
37461318 |
| Submission date |
Mar 08, 2023 |
| Last update date |
Feb 14, 2024 |
| Contact name |
Astrid Wachter |
| E-mail(s) |
astrid.wachter@abbvie.com
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| Organization name |
AbbVie Deutschland GmbH & Co. KG
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| Street address |
Knollstrasse
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| City |
Ludwigshafen |
| ZIP/Postal code |
67061 |
| Country |
Germany |
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| Platforms (1) |
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| Samples (58)
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| Relations |
| BioProject |
PRJNA942219 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE226901_counts.txt.gz |
1.8 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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