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Status |
Public on Apr 27, 2017 |
Title |
Alternative poly(A) in Alzheimer's disase |
Organism |
Homo sapiens |
Experiment type |
Expression profiling by high throughput sequencing
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Summary |
Alternative polyadenylation (APA) contributes to post-transcriptional regulation, but its role in Alzheimer’s disease (AD) is largely unknown. Using high-resolution SQUARE multiple 3’ primer-based sequencing, we discovered massive APA differences in temporal gyrus tissues from demented AD patients compared to either healthy controls or non-demented donors with AD neuropathology (NDWP). Advanced statistics, microfluidics RT-PCR and protein measurements validated known and novel APA-modified 3’-intact transcripts. Moreover, APA modifications, more than total transcript counts, distinguished AD patients from both controls and NDWP donors and identified cell type-characteristic, cognition-associated and neuropathology-related changes. AD-enhanced APA variants included known therapeutic targets of brain, vascular and autoimmune disorders, predicting co-involvement of these target genes in AD progression; AD/NDWP increases in 3’-intact proteinopathy-related hnRNP mRNAs were inversely associated with protein decreases, whereas NDWP-potentiated cognition was accompanied by distinct ATP and mitochondrial variants. APA variations thus provide a novel resource of unique value for both basic and translational neuroscience researchers.
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Overall design |
Examination of poly adenylation sites in brain tissues of Alzheimer's disease patients, non-demented with Alzheimer's disease like pathology and non-demented without Alzheimer's disease like pathology.
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Contributor(s) |
Barbash S, Soreq H, Seitz A |
Citation(s) |
28630030 |
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Submission date |
Apr 29, 2014 |
Last update date |
May 15, 2019 |
Contact name |
Shahar Barbash |
E-mail(s) |
barbashshahar@gmail.com
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Organization name |
The Rockefeller University
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Lab |
Tom Sakmar
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Street address |
1230 York Ave
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City |
New York |
State/province |
NY |
ZIP/Postal code |
10065 |
Country |
USA |
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Platforms (1) |
GPL16288 |
AB 5500xl Genetic Analyzer (Homo sapiens) |
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Samples (24)
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Relations |
BioProject |
PRJNA245791 |
SRA |
SRP041534 |