{"doi":"10.1016/j.celrep.2020.108224","title":"PICALM Rescues Endocytic Defects Caused by the Alzheimer’s Disease Risk Factor APOE4","abstract":"The ε4 allele of apolipoprotein E (APOE4) is a genetic risk factor for many diseases, including late-onset Alzheimer's disease (AD). We investigate the cellular consequences of APOE4 in human iPSC-derived astrocytes, observing an endocytic defect in APOE4 astrocytes compared with their isogenic APOE3 counterparts. Given the evolutionarily conserved nature of endocytosis, we built a yeast model to identify genetic modifiers of the endocytic defect associated with APOE4. In yeast, only the expression of APOE4 results in dose-dependent defects in both endocytosis and growth. We discover that increasing expression of the early endocytic adaptor protein Yap1802p, a homolog of the human AD risk factor PICALM, rescues the APOE4-induced endocytic defect. In iPSC-derived human astrocytes, increasing expression of PICALM similarly reverses endocytic disruptions. Our work identifies a functional interaction between two AD genetic risk factors-APOE4 and PICALM-centered on the conserved biological process of endocytosis.","journal":"Cell Reports","year":2020,"id":56748,"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":83,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9557,"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":84814,"name":"Grzegorz Sienski","orcid":"0000-0002-2730-7710","position":1,"is_corresponding":false},{"id":17176,"name":"Julia Maeve Bonner","orcid":"0000-0003-3551-9972","position":2,"is_corresponding":false},{"id":17178,"name":"Yuan-Ta Lin","orcid":null,"position":3,"is_corresponding":false},{"id":295165,"name":"Jinsoo Seo","orcid":"0000-0001-6432-6964","position":4,"is_corresponding":false},{"id":84821,"name":"Valeriya Baru","orcid":"0000-0001-8518-9313","position":5,"is_corresponding":false},{"id":296759,"name":"Aftabul Haque","orcid":null,"position":6,"is_corresponding":false},{"id":84820,"name":"Blerta Milo","orcid":null,"position":7,"is_corresponding":false},{"id":11610,"name":"Leyla Anne Akay","orcid":"0000-0002-5944-2466","position":8,"is_corresponding":false},{"id":71430,"name":"Agnese Graziosi","orcid":"0000-0002-4992-7902","position":9,"is_corresponding":false},{"id":296760,"name":"Yelena Freyzon","orcid":null,"position":10,"is_corresponding":false},{"id":295166,"name":"Dirk Landgraf","orcid":"0000-0001-9353-4738","position":11,"is_corresponding":false},{"id":296761,"name":"William R. Hesse","orcid":null,"position":12,"is_corresponding":false},{"id":296762,"name":"Julie S. Valastyan","orcid":null,"position":13,"is_corresponding":false},{"id":263329,"name":"M. Inmaculada Barrasa","orcid":"0000-0003-3393-4814","position":14,"is_corresponding":false},{"id":11618,"name":"Li-Huei Tsai","orcid":"0000-0003-1262-0592","position":15,"is_corresponding":false},{"id":84824,"name":"Susan Lindquist","orcid":null,"position":16,"is_corresponding":false},{"id":84815,"name":"Priyanka Narayan","orcid":"0000-0002-9328-4959","position":0,"is_corresponding":true}],"reference_count":50,"raw_metadata":null,"created_at":"2026-07-18T21:06:09.605575Z","pmid":"33027662","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":[]}