{"doi":"10.1101/2020.04.15.041376","title":"Deciphering cellular transcriptional alterations in Alzheimer’s disease brains","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.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2020,"id":120672,"datarank":0.4949905149511482,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.1496027510020413,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.1496027510020413,"corpus_percentile":61.251643846213355,"corpus_rank":5010,"citation_count":9,"citer_count":8,"citers_with_citation_signal":5,"citers_with_endowment":5,"datacite_reuse_total":0,"is_dataset":true,"is_dataset_confidence":0.6342,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":232915,"name":"Mariet Allen","orcid":"0000-0002-2685-427X","position":1,"is_corresponding":false},{"id":308844,"name":"Shaoyu Li","orcid":"0000-0003-1687-619X","position":2,"is_corresponding":false},{"id":308845,"name":"Zachary Quicksall","orcid":"0000-0002-8791-0925","position":3,"is_corresponding":false},{"id":308846,"name":"Tulsi Patel","orcid":"0000-0002-2797-1443","position":4,"is_corresponding":false},{"id":308847,"name":"Troy Carnwath","orcid":"0000-0003-2703-9047","position":5,"is_corresponding":false},{"id":308848,"name":"Joseph S. Reddy","orcid":"0000-0002-1783-4453","position":6,"is_corresponding":false},{"id":308849,"name":"Minerva M. Carrasquillo","orcid":"0000-0002-3231-9134","position":7,"is_corresponding":false},{"id":310055,"name":"Sarah Lincoln","orcid":null,"position":8,"is_corresponding":false},{"id":308850,"name":"Thuy Nguyen","orcid":"0000-0001-8879-7090","position":9,"is_corresponding":false},{"id":310056,"name":"Kimberly G. Malphrus","orcid":null,"position":10,"is_corresponding":false},{"id":54753,"name":"Dennis W. Dickson","orcid":"0000-0001-7189-7917","position":11,"is_corresponding":false},{"id":308851,"name":"Julia E. Crook","orcid":"0000-0001-9932-925X","position":12,"is_corresponding":false},{"id":230891,"name":"Yan W. Asmann","orcid":"0000-0002-8896-2647","position":13,"is_corresponding":false},{"id":776,"name":"Nilüfer Ertekin‐Taner","orcid":"0000-0003-4436-8889","position":14,"is_corresponding":false},{"id":230880,"name":"Xue Wang","orcid":"0000-0003-1964-4124","position":0,"is_corresponding":true}],"reference_count":58,"raw_metadata":null,"created_at":"2026-07-18T23:14:38.147936Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}