ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2025
Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease.
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Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed.
- DYRK1A and Parkinson's disease, facts and hypotheses.Neurobiology of disease · 2026Review
- Tau368 improves p-tau diagnostic accuracy for FTLD-tau from FTLD-TDP.Acta neuropathologica · 2026Article
- Blood-Based Biomarkers Predict Differential Longitudinal Decline in Alzheimer's Disease Psychosis: Evidence from Two Cohorts.medRxiv : the preprint server for health sciences · 2026Article
- Imaging and plasma biomarkers for pathological accumulation in Down syndrome.Brain : a journal of neurology · 2026Article
- Age-related behavioral and molecular landmarks in new mouse models for studying Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Tau pathological activity in plasma before the onset of symptomatic Alzheimer's disease.medRxiv : the preprint server for health sciences · 2026Article
- Head-to-head comparison of plasma p-tau217 immunoassays for incipient Alzheimer's disease in community cohorts.Alzheimer's research & therapy · 2026Article
- Targeting dual specificity tyrosine-phosphorylation-regulated kinase 1A mitigates tauopathy and enhances recovery after repetitive head injury.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Plasma p-tau212 identifies cognitively unimpaired individuals with emerging amyloid-β pathology.Journal of neurology · 2025Article
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Plasma p-tau217 as a biomarker of Alzheimer's disease pathology in individuals with Down syndrome.Nature communications · 2025Observational
- Tau pathology differs by sex in Alzheimer's disease in Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Biomarker Profile of Alzheimer's Disease for Disease-Modifying Treatment Eligibility: Questions and Debates.International journal of molecular sciences · 2025Review
- Cargo of small extracellular vesicles from neuronal origin shows progression of dementia in individuals with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The Down Alzheimer Barcelona Neuroimaging Initiative (DABNI) and its contributions to understanding Alzheimer's disease in Down syndrome: A decade of discovery.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Disease-specific neuropathological alterations of the locus coeruleus in Alzheimer's disease, Down syndrome, and Parkinson's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Plasma p-tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
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Authors and funding
19 authors.
Przemysław R KacInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.ORCID 0000-0001-5083-0924
Daniel AlcoleaSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Laia Montoliu-GayaInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Susana FernándezBarcelona Down Medical Center, Fundació Catalana Síndrome de Down, Carrer del Comte Borrell, Barcelona, Spain.
Juan Lantero RodriguezInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Lucía MaureSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Fernando González-OrtizInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Bessy BenejamSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Michael TurtonBioventix Plc, Farnham, UK.
Isabel BarroetaSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Peter HarrisonBioventix Plc, Farnham, UK.
Laura VidelaSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Nicholas J AshtonInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Alberto LleóSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Henrik ZetterbergInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
María Carmona-IraguiSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Thomas K KarikariInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Juan ForteaSant Pau Memory Unit, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain.
Kaj BlennowInstitute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, The Sahlgrenska Academy at University of Gothenburg, Mölndal, Sweden.
Funding
Vascular Moderators of the Impact of Alzheimer's Pathology in the Young-OldP01AG025204 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI HOWARD J AIZENSTEIN, Ann D. Cohen · 2005 to 2026
$56.5MLongitudinal multicenter head-to-head harmonization of tau PET tracersR01AG073267 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BAKER, SUZANNE L, PASCOAL, THARICK · 2021 to 2025
$41.1MResearch Education ComponentP30AG066468 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI C. Elizabeth Shaaban · 2020 to 2026
$29.4MInvestigating Gains in Neurocognition in an Intervention Trial of Exercise SupplementR01AG053952 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BURNS, JEFFREY MURRAY, ERICKSON, KIRK I · 2016 to 2020
$27.5MMild Cognitive Impairment: A Prospective Community StudyR37AG023651 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu, MARY GANGULI · 2021 to 2026
$18.2MPlasma brain-derived tau: a novel Alzheimer’s disease-type neurodegeneration biomarker with potential to complete the AT(N) scheme in bloodR01AG083874 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Thomas K Karikari · 2023 to 2026
$14.5MThe RAW Brain - The Effect of Rumination, Anxiety and Worry on Aging and Dementia RiskR01MH108509 · NIMH · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Carmen Andreescu · 2016 to 2026
$10.6MPredictors of Altered CNS Structure, Function, and Connectomics in the Elderly using a Health Disparities FrameworkR01AG072641 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Ann D. Cohen · 2022 to 2026
$9.6MSubclinical vascular disease and AD pathology in the transition from midlife to old ageRF1AG052525 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI LOPEZ, OSCAR L., REIS, STEVEN E · 2018 to 2018
$9.3MRoles of Gray Matter Brain Aging and Small Vessel Disease in AD PathophysiologyRF1AG025516 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI AIZENSTEIN, HOWARD J, VILLEMAGNE, VICTOR LUIS · 2014 to 2021
$9.0MDS-ARC: A Remote Digital Cognitive Assessment for Down Syndrome-Associated Alzheimer's DiseaseR01AG081394 · NIA · WASHINGTON UNIVERSITY · PI Jason J Hassenstab · 2023 to 2026
$6.0MThe Role of Inflammation and NGF Dysfunction in the Evolution of Alzheimer Disease Pathology in Down Syndrome-RevisionRF1AG056850 · NIA · UNIVERSITY OF CALIFORNIA-IRVINE · PI BUSCIGLIO, JORGE A, CUELLO, A CLAUDIO · 2018 to 2020
$5.9MÅhlén-stiftelsenAlzheimerfonden #AF-930351Alzheimerfonden #AF-939721Alzheimerfonden #AF-968270Alzheimerfonden and #AF-994551Alzheimer's Association #AARF-21-850325Alzheimer's Drug Discovery Foundation #201809-2016862Anna-Lisa och Bror Björnssons StiftelseBrightFocus Foundation A2022015FCentro de Investigación Biomédica en Red sobre Enfermedades NeurodegenerativasCure Alzheimer's FundDemensfondenDemensförbundetDepartament de Salut, Generalitat de CatalunyaEmil och Wera Cornells StiftelseEU Joint Programme - Neurodegenerative Disease Research JPND2019-466-236European Regional Development FundFondation pour la Recherche sur AlzheimerGun och Bertil Stohnes StiftelseHORIZON EUROPE Framework Programme H2020-SC1-BHC-2018-2020HORIZON EUROPE Marie Sklodowska-Curie Actions 860197HORIZON EUROPE Reforming and enhancing the European Research and Innovation system 101053962Instituto de Salud Carlos III INT21/00073Instituto de Salud Carlos III PI20/01473Instituto de Salud Carlos III PI23/01786Kirsten og Freddy Johansens FondNIA NIH HHS P01 AG025204NIA NIH HHS P30 AG066468NIA NIH HHS R01 AG053952NIA NIH HHS R01 AG072641NIA NIH HHS R01 AG073267NIA NIH HHS R01 AG075336NIA NIH HHS R01 AG081394NIA NIH HHS R01 AG083874NIA NIH HHS R21 AG056974NIA NIH HHS R37 AG023651NIA NIH HHS R61 AG066543NIA NIH HHS RF1 AG025516NIA NIH HHS RF1 AG052525NIA NIH HHS RF1 AG056850NIA NIH HHS RF1 AG061566NIH HHS R01 AG056850NIH HHS R01 AG061566NIH HHS R01 AG081394NIH HHS R21 AG056974NIH HHS R61AG066543NIMH NIH HHS R01 MH108509NIMH NIH HHS R01 MH121619Olav Thon StiftelsenPla Estratègic de Recerca i Innovació en SalutStiftelsen för Gamla Tjänarinnorthe Aina (Ann) Wallströms and Mary-Ann Sjöbloms stiftelsenThe Bluefield Projectthe Fondo de Investigaciones SanitarioUCLH Biomedical Research CentreVetenskapsrådet #2021-03244
Abstract
backgroundAll 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.
methodsUsing single molecule array (Simoa) technology, we tested p-tau212 and p-tau181 (n = 245 for plasma, n = 114 matching cerebrospinal fluid [CSF] samples).
resultsWe 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.
Indexed as
Alzheimer DiseaseDown Syndrometau ProteinsAdultAgedAmyloid beta-PeptidesBiomarkersCognitive DysfunctionDyrk KinasesFemaleHumansMaleMiddle AgedPhosphorylationPositron-Emission TomographyAmyloid beta-PeptidesBiomarkersDyrk KinasesMAPT protein, humantau ProteinsAlzheimer´s diseaseCSF biomarkersDABNIDown syndromeDYRK1Aplasma biomarkersp‐tau212SimoaSPIN
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