{"doi":"10.1002/alz.70172","title":"Plasma p‐tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease","abstract":"BACKGROUND: All individuals with Down syndrome (DS) will develop full-blown Alzheimer´s disease (AD) pathology by age 40. Several genes encoded in chromosome 21, including dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A), have been proven to contribute to the pathology. Phosphorylation of tau at threonine-212 (p-tau212) is very sensitive to DYRK1A phosphorylation and is increased in DSAD brain lysates. Here, we assessed the potential of this biomarker in DSAD and sporadic AD. METHODS: Using single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples). RESULTS: We have confirmed that the levels of plasma p-tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p-tau212 started increasing approximately when people became amyloid positron emission tomography positive. DISCUSSION: Plasma p-tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD. HIGHLIGHTS: Plasma p-tau212 is increased in the Down syndrome (DS) population. Plasma p-tau212 increases ≈15 years before the disease onset in DSAD. Plasma p-tau212 accurately differentiates between control and disease groups. Plasma p-tau212 accurately differentiates amyloid beta (Aβ)+ and Aβ- participants.","journal":"Alzheimer s & Dementia","year":2025,"id":511262,"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":16,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9699,"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":232612,"name":"Daniel Alcolea","orcid":"0000-0002-3819-3245","position":1,"is_corresponding":false},{"id":636000,"name":"Laia Montoliu‐Gaya","orcid":"0000-0001-7684-6318","position":2,"is_corresponding":false},{"id":833759,"name":"Susana Fernández","orcid":"0000-0002-9777-1156","position":3,"is_corresponding":false},{"id":241106,"name":"Juan Lantero‐Rodriguez","orcid":"0000-0002-7426-678X","position":4,"is_corresponding":false},{"id":1369879,"name":"Lucía Maure","orcid":null,"position":5,"is_corresponding":false},{"id":839573,"name":"Fernando González‐Ortiz","orcid":"0000-0001-7897-9456","position":6,"is_corresponding":false},{"id":232594,"name":"Bessy Benejam","orcid":"0000-0002-6789-8615","position":7,"is_corresponding":false},{"id":843049,"name":"Michael Turton","orcid":null,"position":8,"is_corresponding":false},{"id":232596,"name":"Isabel Barroeta","orcid":"0000-0003-2764-7923","position":9,"is_corresponding":false},{"id":1274962,"name":"Peter Harrison","orcid":"0000-0001-7526-4834","position":10,"is_corresponding":false},{"id":232595,"name":"Laura Videla","orcid":"0000-0002-9748-8465","position":11,"is_corresponding":false},{"id":241104,"name":"Nicholas J. Ashton","orcid":"0000-0002-3579-8804","position":12,"is_corresponding":false},{"id":27613,"name":"Alberto Lleó","orcid":"0000-0002-2568-5478","position":13,"is_corresponding":false},{"id":27601,"name":"Henrik Zetterberg","orcid":"0000-0003-3930-4354","position":14,"is_corresponding":false},{"id":232593,"name":"María Carmona‐Iragui","orcid":"0000-0001-6914-2339","position":15,"is_corresponding":false},{"id":241105,"name":"Thomas K. Karikari","orcid":"0000-0003-1422-4358","position":16,"is_corresponding":false},{"id":232591,"name":"Juan Fortea","orcid":"0000-0002-1340-638X","position":17,"is_corresponding":false},{"id":27600,"name":"Kaj Blennow","orcid":"0000-0002-1890-4193","position":18,"is_corresponding":false},{"id":841866,"name":"Przemysław R. Kac","orcid":"0000-0001-5083-0924","position":0,"is_corresponding":true}],"reference_count":41,"raw_metadata":null,"created_at":"2026-07-19T02:47:55.918021Z","pmid":"40275833","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":[]}