{"doi":"10.1101/2021.03.03.433580","title":"Neuronal ROS-Induced Glial Lipid Droplet Formation is Altered by Loss of Alzheimer’s Disease-associated Genes","abstract":"Summary A growing list of Alzheimer’s disease (AD) genetic risk factors is being identified, but the contribution of these genetic mutations to disease remains largely unknown. Accumulating data support a role of lipid dysregulation and excessive ROS in the etiology of AD. Here, we identified cell-specific roles for eight AD risk-associated genes in ROS-induced glial lipid droplet (LD) formation. We demonstrate that ROS-induced glial LD formation requires two ABCA transporters ( ABCA1 and ABCA7 ) in neurons, the APOE receptor ( LRP1 ), endocytic genes ( PICALM , CD2AP , and AP2A2 ) in glia, and retromer genes ( VPS26 and VPS35 ) in both neurons and glia. Moreover, ROS strongly enhances Aβ42-toxicity in flies and Aβ42-plaque formation in mice. Finally, an ABCA1-activating peptide restores glial LD formation in the APOE4-associated loss of LD. This study places AD risk factors in a neuron-to-glia lipid transfer pathway with a critical role in protecting neurons from ROS-induced toxicity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":213955,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9568,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":356020,"name":"Scott Barish","orcid":"0000-0001-7346-3207","position":1,"is_corresponding":false},{"id":625821,"name":"Isha Ralhan","orcid":"0000-0002-6890-2620","position":2,"is_corresponding":false},{"id":625822,"name":"Jinlan Chang","orcid":"0009-0005-4751-1603","position":3,"is_corresponding":false},{"id":625823,"name":"Lindsey D. Goodman","orcid":"0000-0002-9255-3811","position":4,"is_corresponding":false},{"id":626971,"name":"Jake G. Harland","orcid":null,"position":5,"is_corresponding":false},{"id":254710,"name":"Paul C. Marcogliese","orcid":"0000-0002-8011-7852","position":6,"is_corresponding":false},{"id":625824,"name":"Jan O. Johansson","orcid":"0000-0002-3576-2748","position":7,"is_corresponding":false},{"id":625825,"name":"Maria S. Ioannou","orcid":"0000-0001-6252-8626","position":8,"is_corresponding":false},{"id":20909,"name":"Hugo J. Bellen","orcid":"0000-0001-5992-5989","position":9,"is_corresponding":false},{"id":400172,"name":"Matthew J. Moulton","orcid":"0000-0003-0228-7669","position":0,"is_corresponding":true}],"reference_count":163,"raw_metadata":null,"created_at":"2026-07-18T23:52:41.672172Z","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":[]}