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Deciphering cellular transcriptional alterations in Alzheimer’s disease brains
- Source :
- Molecular Neurodegeneration, Vol 15, Iss 1, Pp 1-15 (2020)
- Publication Year :
- 2020
- Publisher :
- BMC, 2020.
-
Abstract
- Abstract Large-scale brain bulk-RNAseq studies identified molecular pathways implicated in Alzheimer’s disease (AD), however these findings can be confounded by cellular composition changes in bulk-tissue. To identify cell intrinsic gene expression alterations of individual cell types, we designed a bioinformatics pipeline and analyzed three AD and control bulk-RNAseq datasets of temporal and dorsolateral prefrontal cortex from 685 brain samples. We detected cell-proportion changes in AD brains that are robustly replicable across the three independently assessed cohorts. We applied three different algorithms including our in-house algorithm to identify cell intrinsic differentially expressed genes in individual cell types (CI-DEGs). We assessed the performance of all algorithms by comparison to single nucleus RNAseq data. We identified consensus CI-DEGs that are common to multiple brain regions. Despite significant overlap between consensus CI-DEGs and bulk-DEGs, many CI-DEGs were absent from bulk-DEGs. Consensus CI-DEGs and their enriched GO terms include genes and pathways previously implicated in AD or neurodegeneration, as well as novel ones. We demonstrated that the detection of CI-DEGs through computational deconvolution methods is promising and highlight remaining challenges. These findings provide novel insights into cell-intrinsic transcriptional changes of individual cell types in AD and may refine discovery and modeling of molecular targets that drive this complex disease.
Details
- Language :
- English
- ISSN :
- 17501326
- Volume :
- 15
- Issue :
- 1
- Database :
- Directory of Open Access Journals
- Journal :
- Molecular Neurodegeneration
- Publication Type :
- Academic Journal
- Accession number :
- edsdoj.73a909cc5a9e407690b5d36b6071548c
- Document Type :
- article
- Full Text :
- https://doi.org/10.1186/s13024-020-00392-6