التفاصيل البيبلوغرافية
| العنوان: |
Transcriptomic signatures of regional selective vulnerability in ALS and FTLD‐TDP |
| المؤلفون: |
Spencer, Barbara E, Phatnani, Hemali, Lee, Eddie B, Irwin, David J., McMillan, Corey T |
| المصدر: |
Alzheimer's & Dementia ; volume 19, issue S12 ; ISSN 1552-5260 1552-5279 |
| بيانات النشر: |
Wiley |
| سنة النشر: |
2023 |
| المجموعة: |
Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: |
Background Differential gene expression in the brain has been identified in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration with TDP‐43 (FTLD‐TDP) relative to controls. However, direct comparisons of ALS and FTLD‐TDP are rare. We hypothesize that identification of distinct transcriptomic signatures between ALS and FTLD‐TDP may provide insight into regional selective vulnerability of TDP‐43. Here, we directly compare gene expression in frontal cortex between FTLD‐TDP and ALS cases, accounting for cell‐type proportion differences due to neurodegeneration. Method Frontal cortex RNA‐seq samples passing extensive quality control metrics were downloaded from the New York Genome Center ALS Consortium, including non‐neurological controls (n = 42) and individuals with neuropathological diagnoses of ALS (n = 118) or FTLD‐TDP (n = 27). A total of 59,782 genes were quantified for each sample. Scaden was used to deconvolve this bulk RNA‐seq data into cell type proportions. Infrequently expressed genes were filtered and data was normalized by total count. Generalized linear model estimates of dispersion were calculated accounting for potential confounders including cell type proportions, RIN, contributing site, age at death, and sex to identify differentially expressed genes (DEGs) between ALS and FTLD‐TDP as well as each neurological group relative to controls. A gene ontology enrichment analysis for biological processes was performed for each DEG set. We report DEGs and enrichment surviving FDR p<0.05. Result 653 DEGs were identified in FTLD‐TDP compared to ALS within the frontal cortex samples. The majority of these DEGs were also differentially expressed between only one of these neurological groups and controls. However, 281 of these DEGs were uniquely differentially expressed in ALS compared to FTLD‐TDP, not differentially expressed between either neurological group and controls. Gene ontology enrichment analyses for biological processes revealed that the 198 genes uniquely ... |
| نوع الوثيقة: |
article in journal/newspaper |
| اللغة: |
English |
| DOI: |
10.1002/alz.078758 |
| الاتاحة: |
http://dx.doi.org/10.1002/alz.078758 |
| Rights: |
http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: |
edsbas.E02037A0 |
| قاعدة البيانات: |
BASE |