{"doi":"10.1002/alz.70408","title":"Age and sex are associated with Alzheimer's disease neuropathology in Down syndrome","abstract":"INTRODUCTION: This study investigates the association of age and biological sex with Alzheimer's disease (AD) neuropathology in Down syndrome (DS). METHODS: We examined the frontal/occipital cortex in people with DS (n = 14/13, 1-39 years), DS with AD (DSAD) neuropathology (n = 18/19, 42-61 years), late-onset AD (n = 15/16, 72-96 years), and age-matched controls (n = 50/47)(n = 156). The area occupied by AT8 and 6E10 immunolabeling, representing tangle and plaque loads, respectively, was used for segmented linear regression analyses. RESULTS: There was elevated neuropathology after age 35 in DSAD, with inflection points at ∼31 years (amyloid-β [Aβ]) and ∼28 (phosphorylated tau [p-tau]) in the frontal cortex and ∼36 years (both Aβ and p-tau) in the occipital cortex. Occipital p-tau was higher in women relative to men with DS. Aβ and p-tau pathology were correlated in women with DS but not in men with DS in the occipital cortex. DISCUSSION: Women with DS may show a more advanced stage of tau pathology relative to men with DS. HIGHLIGHTS: Amyloid-β (Aβ) and phosphorylated tau (p-tau) Alzheimer's disease (AD) pathology emerge after 30 years of age in the frontal cortex, followed 7 years later by pathology in the occipital cortex in Down syndrome (DS). Women with DS show a more rapid progression of AD neuropathology seen by trends in higher p-tau relative to men, despite similar levels of Aβ. Women with DS show a stronger association between Aβ and tau in the occipital but not frontal cortex relative to men with DS, independent of age.","journal":"Alzheimer s & Dementia","year":2025,"id":523898,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.7986,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1323540,"name":"Phong Ngo","orcid":null,"position":1,"is_corresponding":false},{"id":843577,"name":"Jesse R. Pascual","orcid":"0000-0002-3307-0887","position":2,"is_corresponding":false},{"id":1397363,"name":"Freddy Gonzalez","orcid":null,"position":3,"is_corresponding":false},{"id":464672,"name":"Michael Phelan","orcid":null,"position":4,"is_corresponding":false},{"id":1323541,"name":"Sierra Wright","orcid":null,"position":5,"is_corresponding":false},{"id":888599,"name":"Jordan P. Harp","orcid":"0000-0003-2089-0883","position":6,"is_corresponding":false},{"id":245004,"name":"Frederick A. Schmitt","orcid":"0000-0003-4315-2488","position":7,"is_corresponding":false},{"id":270467,"name":"Florence Lai","orcid":"0000-0003-4354-0624","position":8,"is_corresponding":false},{"id":769479,"name":"Patrick J. Lao","orcid":"0000-0003-2243-3547","position":9,"is_corresponding":false},{"id":270469,"name":"Adam M. Brickman","orcid":"0000-0002-5125-8226","position":10,"is_corresponding":false},{"id":98,"name":"Julia Kofler","orcid":"0000-0003-4298-7328","position":11,"is_corresponding":false},{"id":422876,"name":"Miloš D. Ikonomović","orcid":"0000-0002-8745-3293","position":12,"is_corresponding":false},{"id":270466,"name":"Elizabeth Head","orcid":"0000-0003-1115-6396","position":13,"is_corresponding":false},{"id":839621,"name":"Elizabeth J. Andrews","orcid":"0000-0003-2463-5708","position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:50:07.396155Z","pmid":"40673442","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":[]}