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Several genes encoded in chromosome 21, including dual\u2010specificity tyrosine phosphorylation\u2010regulated kinase 1A (\n                      <jats:italic>DYRK1A<\/jats:italic>\n                      ), have been proven to contribute to the pathology. Phosphorylation of tau at threonine\u2010212 (p\u2010tau212) 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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Using single molecule array (Simoa) technology, we tested p\u2010tau212 and p\u2010tau181 (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0245 for plasma,\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a0114 matching cerebrospinal fluid [CSF] samples).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>We have confirmed that the levels of plasma p\u2010tau212 are increased in the DS population and sporadic AD cases, including prodromal and mild cognitive impairment states. Plasma p\u2010tau212 started increasing approximately when people became amyloid positron emission tomography positive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>Plasma p\u2010tau212 might have utility for theragnostics, monitoring therapy efficacy, and as a target engagement biomarker in clinical trials both in sporadic and DSAD.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>Plasma p\u2010tau212 is increased in the Down syndrome\u00a0(DS) population.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma p\u2010tau212 increases \u224815 years before the disease onset in DSAD.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma p\u2010tau212 accurately differentiates between control and disease groups.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Plasma p\u2010tau212 accurately differentiates amyloid beta (A\u03b2)+ and A\u03b2\u2212 participants.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70172","type":"journal-article","created":{"date-parts":[[2025,4,25]],"date-time":"2025-04-25T04:14:18Z","timestamp":1745554458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Plasma p\u2010tau212 as a biomarker of sporadic and Down syndrome Alzheimer's disease"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5083-0924","authenticated-orcid":false,"given":"Przemys\u0142aw R.","family":"Kac","sequence":"first","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Alcolea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center for Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) Av. Monforte de Lemos  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laia","family":"Montoliu\u2010Gaya","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susana","family":"Fern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down Carrer del Comte Borrell  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Lantero","family":"Rodriguez","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luc\u00eda","family":"Maure","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center for Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) Av. Monforte de Lemos  Madrid Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down Carrer del Comte Borrell  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando","family":"Gonz\u00e1lez\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience and Physiology Department of Psychiatry and Neurochemistry The Sahlgrenska Academy at University of Gothenburg  M\u00f6lndal Sweden"},{"name":"Clinical Neurochemistry Laboratory Sahlgrenska University Hospital  M\u00f6lndal Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bessy","family":"Benejam","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Barcelona Down Medical Center Fundaci\u00f3 Catalana S\u00edndrome de Down Carrer del Comte Borrell  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Turton","sequence":"additional","affiliation":[{"name":"Bioventix Plc  Farnham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Barroeta","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit Hospital de la Santa Creu i Sant Pau Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"},{"name":"Center for Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED) Av. 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