{"doi":"10.1084/jem.20250965","title":"ApoE-calypse tau: ApoE–tau synergy in Alzheimer’s disease","abstract":"<jats:p>Alzheimer’s disease (AD), the most common cause of dementia, is characterized by the accumulation of amyloid-β (Aβ) in senile plaques and abnormally hyperphosphorylated tau proteins in neurofibrillary tangles. While much of the research has focused on Aβ, tau-mediated neurodegeneration is more closely associated with synaptic loss and cognitive decline in AD, emphasizing the need for a deeper understanding of tau pathology. In this context, the interaction between tau and APOE, particularly the main genetic risk factor for AD APOE ε4, remains underexplored. APOE encodes apolipoprotein E (apoE), a protein important in lipid metabolism. In addition to promoting Aβ deposition, emerging evidence suggests that APOE ε4 exacerbates tau-mediated neurodegeneration and tau-related pathology. This review consolidates current knowledge on the interplay between apoE and tau, highlighting its potential as a key factor in disease progression. Targeting the apoE–tau axis may offer promising therapeutic strategies to address the molecular mechanisms driving AD and primary tauopathies.</jats:p>","journal":"Journal of Experimental Medicine","year":2025,"id":599974,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1537895,"name":"Chiara Bordier","orcid":"0000-0001-9644-683X","position":1,"is_corresponding":false},{"id":1537896,"name":"Léana Kamelher","orcid":"0009-0002-8204-7357","position":2,"is_corresponding":false},{"id":236544,"name":"Jason D. Ulrich","orcid":"0000-0002-4743-926X","position":3,"is_corresponding":false},{"id":27592,"name":"David M. Holtzman","orcid":"0000-0002-3400-0856","position":4,"is_corresponding":false},{"id":236536,"name":"Maud Gratuze","orcid":"0000-0002-1552-8815","position":5,"is_corresponding":false},{"id":902089,"name":"Matthew P. Lennol","orcid":"0000-0002-4021-181X","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ApoE-calypse tau: ApoE–tau synergy in Alzheimer’s disease","abstract":"<jats:p>Alzheimer’s disease (AD), the most common cause of dementia, is characterized by the accumulation of amyloid-β (Aβ) in senile plaques and abnormally hyperphosphorylated tau proteins in neurofibrillary tangles. While much of the research has focused on Aβ, tau-mediated neurodegeneration is more closely associated with synaptic loss and cognitive decline in AD, emphasizing the need for a deeper understanding of tau pathology. In this context, the interaction between tau and APOE, particularly the main genetic risk factor for AD APOE ε4, remains underexplored. APOE encodes apolipoprotein E (apoE), a protein important in lipid metabolism. In addition to promoting Aβ deposition, emerging evidence suggests that APOE ε4 exacerbates tau-mediated neurodegeneration and tau-related pathology. This review consolidates current knowledge on the interplay between apoE and tau, highlighting its potential as a key factor in disease progression. Targeting the apoE–tau axis may offer promising therapeutic strategies to address the molecular mechanisms driving AD and primary tauopathies.</jats:p>","is_dataset_classified":null,"base_score":2.3978952727983707,"endowment":2.3978952727983707,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40856646","pmcid":null,"openalex_id":"https://openalex.org/W4413751181","authors":[],"funders":[],"total_grants":0,"fwci":6.5767,"citation_percentile":0.97312857,"influential_citations":0,"citation_trend":[{"year":2025,"count":3},{"year":2026,"count":7}],"oa_status":"bronze","license":"cc-by","oa_locations":[{"url":"https://rupress.org/jem/article-pdf/222/10/e20250965/1949406/jem_20250965.pdf","host_type":"journal"},{"url":"https://rupress.org/jem/article-pdf/222/10/e20250965/1949406/jem_20250965.pdf","host_type":"publisher"},{"url":"https://rupress.org/jem/article-pdf/doi/10.1084/jem.20250965/1949406/jem_20250965.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1084/jem.20250965","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/40856646","host_type":"repository"},{"url":"https://hal.science/hal-05273417","host_type":"repository"},{"url":"https://hal.science/hal-05326627","host_type":"repository"},{"url":"https://digitalcommons.wustl.edu/oa_4/5872","host_type":"repository"}],"fields_of_study":["Alzheimer's disease research and treatments","Computational Drug Discovery Methods","S100 Proteins and Annexins","Medicine","Biology"],"mesh_terms":["Alzheimer Disease","Animals","Apolipoproteins E","Humans","Amyloid beta-Peptides","tau Proteins"],"keywords":["Apolipoprotein E","Alzheimer's disease","Disease","Medicine","Psychology","Internal medicine","Neuroscience"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T11:53:09.552692Z","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":[]}