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In addition to the intellectual disability associated with DS, adults with DS also have an ultrahigh risk of developing early onset Alzheimer\u2019s disease dementia. DYRK1A, a proline-directed serine\/threonine kinase, whose gene is located on chromosome 21, has recently emerged as a promising plasma biomarker in patients with sporadic Alzheimer\u2019s disease (AD). The protein DYRK1A is truncated in symptomatic AD, the increased truncated form being associated with a decrease in the level of full-length form. Activity-dependent neuroprotective protein (ADNP), a key protein for the brain development, has been demonstrated to be a useful marker for symptomatic AD and disease progression. In this study, we evaluated DYRK1A and ADNP in CSF and plasma of adults with DS and explored the relationship between these proteins. We used mice models to evaluate the effect of DYRK1A overexpression on ADNP levels and then performed a dual-center cross-sectional human study in adults with DS in Barcelona (Spain) and Paris (France). Both cohorts included adults with DS at different stages of the continuum of AD: asymptomatic AD (aDS), prodromal AD (pDS), and AD dementia (dDS). Non-trisomic controls and patients with sporadic AD dementia were included for comparison. Full-form levels of DYRK1A were decreased in plasma and CSF in adults with DS and symptomatic AD (pDS and dDS) compared to aDS, and in patients with sporadic AD compared to controls. On the contrary, the truncated form of DYRK1A was found to increase both in CSF and plasma in adults with DS and symptomatic AD and in patients with sporadic AD with respect to aDS and controls. ADNP levels showed a more complex structure. ADNP levels increased in aDS groups vs. controls, in agreement with the increase in levels found in the brains of mice overexpressing DYRK1A. However, symptomatic individuals had lower levels than aDS individuals. Our results show that the comparison between full-length and truncated-form levels of DYRK1A coupled with ADNP levels could be used in trials targeting pathophysiological mechanisms of dementia in individuals with DS.<\/jats:p>","DOI":"10.3390\/biomedicines10061380","type":"journal-article","created":{"date-parts":[[2022,6,10]],"date-time":"2022-06-10T10:25:12Z","timestamp":1654856712000},"page":"1380","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["DYRK1A and Activity-Dependent Neuroprotective Protein Comparative Diagnosis Interest in Cerebrospinal Fluid and Plasma in the Context of Alzheimer-Related Cognitive Impairment in Down Syndrome Patients"],"prefix":"10.3390","volume":"10","author":[{"given":"Manon","family":"Moreau","sequence":"first","affiliation":[{"name":"CNRS, UMR 8251, Biologie Fonctionnelle et Adaptative (BFA), Universit\u00e9 Paris Cit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Carmona-Iragui","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down, 08029 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9709-5314","authenticated-orcid":false,"given":"Miren","family":"Altuna","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorraine","family":"Dalzon","sequence":"additional","affiliation":[{"name":"CNRS, UMR 8251, Biologie Fonctionnelle et Adaptative (BFA), Universit\u00e9 Paris Cit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Barroeta","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4401-7755","authenticated-orcid":false,"given":"Marie","family":"Vilaire","sequence":"additional","affiliation":[{"name":"Institut M\u00e9dical J\u00e9r\u00f4me Lejeune, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Durand","sequence":"additional","affiliation":[{"name":"Institut M\u00e9dical J\u00e9r\u00f4me Lejeune, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan","family":"Fortea","sequence":"additional","affiliation":[{"name":"Sant Pau Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"},{"name":"Center of Biomedical Investigation Network for Neurodegenerative Diseases (CIBERNED), 28029 Madrid, Spain"},{"name":"Barcelona Down Medical Center, Fundaci\u00f3 Catalana de S\u00edndrome de Down, 08029 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Rebillat","sequence":"additional","affiliation":[{"name":"Institut M\u00e9dical J\u00e9r\u00f4me Lejeune, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathalie","family":"Janel","sequence":"additional","affiliation":[{"name":"CNRS, UMR 8251, Biologie Fonctionnelle et Adaptative (BFA), Universit\u00e9 Paris Cit\u00e9, 75013 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1016\/S1474-4422(10)70112-5","article-title":"Cognitive deficits and associated neurological complications in individuals with Down\u2019s syndrome","volume":"9","author":"Lott","year":"2010","journal-title":"Lancet Neurol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/B978-0-444-54299-1.00006-6","article-title":"Neurological phenotypes for Down syndrome across the life span","volume":"197","author":"Lott","year":"2012","journal-title":"Prog. 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