{"doi":"10.1101/2021.07.13.452239","title":"Co-aggregation with Apolipoprotein E modulates the function of Amyloid-β in Alzheimer’s disease","abstract":"Abstract Which isoforms of apolipoprotein E (apoE) we inherit determine our risk of developing late-onset Alzheimer’s Disease (AD), but the mechanism underlying this link is poorly understood. In particular, the relevance of direct interactions between apoE and amyloid-β (Aβ) remains controversial. Here, single-molecule imaging shows that all isoforms of apoE associate with Aβ in the early stages of aggregation and then fall away as fibrillation happens. ApoE-Aβ co-aggregates account for ∼50% of the mass of soluble Aβ aggregates detected in the frontal cortices of homozygotes with the higher-risk APOE4 gene. Our results connect inherited APOE genotype with the risk of developing AD by demonstrating how, in an isoform- and lipidation-specific way, apoE modulates the aggregation, clearance and toxicity of Aβ. Selectively removing non-lipidated apoE4-Aβ co-aggregates enhances clearance of toxic Aβ by glial cells, and reduces inflammation and membrane damage, demonstrating a clear path to AD therapeutics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":225603,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"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":828351,"name":"Emily E. Prescott","orcid":null,"position":1,"is_corresponding":false},{"id":828026,"name":"Hollie Wareing","orcid":"0000-0003-0785-4116","position":2,"is_corresponding":false},{"id":828027,"name":"Martyna M. Matuszyk","orcid":"0000-0002-9497-6922","position":3,"is_corresponding":false},{"id":828028,"name":"Helen Dakin","orcid":"0000-0003-0571-5892","position":4,"is_corresponding":false},{"id":828029,"name":"Eleni Dimou","orcid":"0000-0003-4885-135X","position":5,"is_corresponding":false},{"id":828352,"name":"Eric Zuo","orcid":null,"position":6,"is_corresponding":false},{"id":828030,"name":"Yu P. Zhang","orcid":"0000-0001-5486-278X","position":7,"is_corresponding":false},{"id":828031,"name":"Jeff Y. L. Lam","orcid":"0000-0001-7408-2342","position":8,"is_corresponding":false},{"id":828032,"name":"John S. H. Danial","orcid":"0000-0002-9882-8441","position":9,"is_corresponding":false},{"id":828353,"name":"Tom Leah","orcid":null,"position":10,"is_corresponding":false},{"id":828033,"name":"Katy Barnes","orcid":"0000-0002-0045-7970","position":11,"is_corresponding":false},{"id":233379,"name":"Michael R. Strickland","orcid":"0000-0002-3899-5651","position":12,"is_corresponding":false},{"id":474994,"name":"Hong Jiang","orcid":"0000-0001-7188-5713","position":13,"is_corresponding":false},{"id":828034,"name":"Peter Thornton","orcid":"0000-0002-2489-3507","position":14,"is_corresponding":false},{"id":828035,"name":"Damian C. Crowther","orcid":"0000-0001-7791-1396","position":15,"is_corresponding":false},{"id":27592,"name":"David M. Holtzman","orcid":"0000-0002-3400-0856","position":16,"is_corresponding":false},{"id":828036,"name":"Simon Bell","orcid":"0000-0002-2781-6478","position":17,"is_corresponding":false},{"id":239154,"name":"Adrian Higginbottom","orcid":null,"position":18,"is_corresponding":false},{"id":557196,"name":"Laura Ferraiuolo","orcid":"0000-0001-9118-5714","position":19,"is_corresponding":false},{"id":828037,"name":"Heather Mortiboys","orcid":"0000-0001-6439-0579","position":20,"is_corresponding":false},{"id":828038,"name":"Stephen B. Wharton","orcid":"0000-0003-2785-333X","position":21,"is_corresponding":false},{"id":828039,"name":"Rohan T. Ranasinghe","orcid":"0000-0001-9227-4110","position":22,"is_corresponding":false},{"id":296221,"name":"David Klenerman","orcid":"0000-0001-7116-6954","position":23,"is_corresponding":false},{"id":331618,"name":"Suman De","orcid":"0000-0003-1675-0773","position":24,"is_corresponding":false},{"id":828025,"name":"Zengjie Xia","orcid":"0000-0002-5977-9691","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-18T23:54:26.581453Z","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":[]}