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| Status |
Public on Jan 27, 2022 |
| Title |
Endotype reversal as a novel strategy for screening drugs targeting familial Alzheimer's disease |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
While amyloid-β (Aβ) plaques are considered a hallmark of Alzheimer's disease, clinical trials focused on targeting gamma secretase, an enzyme involved in aberrant Aβ peptide production, have not led to amelioration of AD symptoms or synaptic dysregulation. Screening strategies based on mechanistic, multi-omics approaches that go beyond pathological readouts can aid in the evaluation of therapeutics. Using early-onset Alzheimer's (EOFAD) disease patient lineage PSEN1A246E iPSC-derived neurons, we performed RNA-seq to characterize AD-associated endotypes, which are in turn used as a screening evaluation metric for two gamma secretase drugs, the inhibitor Semagacestat and the modulator BPN-15606.
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| Overall design |
hiPSC-derived neurons were generated from donor non-demented control (NDC) or EOFAD-causing psen1 A246E patients. Total RNA was extracted from: NDC hiPSC-derived neurons treated with DMSO (vehicle), n=2; PSEN1A246E hiPSC-derived neurons treated with DMSO (vehicle), n=3; PSEN1A246E hiPSC-derived neurons treated with BPN-15606 (G), n=3; and PSEN1A246E hiPSC-derived neurons treated with Semagacestat (S), n=3. Samples were sequenced on a illumina HiSeq 4000 generating Paired End, 75bp reads.
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| Contributor(s) |
Caldwell AB, Liu Q, Zhang C, Schroth GP, Galasko DR, Tanzi RE, Yuan SH, Wagner SL, Subramaniam S |
| Citation(s) |
35084109 |
| Submission date |
Mar 03, 2017 |
| Last update date |
Jan 27, 2022 |
| Contact name |
Shankar Subramaniam |
| Organization name |
University of California, San Diego
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| Department |
Department of Bioengineering
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| Street address |
9500 Gilman Drive
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| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92093-0412 |
| Country |
USA |
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| Platforms (1) |
| GPL20301 |
Illumina HiSeq 4000 (Homo sapiens) |
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| Samples (11)
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| Relations |
| BioProject |
PRJNA377888 |
| SRA |
SRP101349 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE95673_NDC_PS1_GSM_GSI_FPKM.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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