{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T22:11:55Z","timestamp":1792793515914,"version":"4.5.0"},"reference-count":134,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Epidemiological evidence suggests that by the age of 40 years, all individuals with Down syndrome (DS) have Alzheimer\u2019s disease (AD) neuropathology. Clinical diagnosis of dementia by cognitive assessment is complex in these patients due to the pre-existing and varying intellectual disability, which may mask subtle declines in cognitive functioning. Cerebrospinal fluid (CSF) and positron emission tomography (PET) biomarkers, although accurate, are expensive, invasive, and particularly challenging in such a vulnerable population. The advances in ultra-sensitive detection methods have highlighted blood biomarkers as a valuable and realistic tool for AD diagnosis. Studies with DS patients have proven the potential blood-based biomarkers for sporadic AD (amyloid-\u03b2, tau, phosphorylated tau, and neurofilament light chain) to be useful in this population. In addition, biomarkers related to other pathologies that could aggravate dementia progression\u2014such as inflammatory dysregulation, energetic imbalance, or oxidative stress\u2014have been explored. This review serves to provide a brief overview of the main findings from the limited neuroimaging and CSF studies, outline the current state of blood biomarkers to diagnose AD in patients with DS, discuss possible past limitations of the research, and suggest considerations for developing and validating blood-based biomarkers in the future.<\/jats:p>","DOI":"10.3390\/jcm10163639","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"3639","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Blood Biomarkers for Alzheimer\u2019s Disease in Down Syndrome"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7684-6318","authenticated-orcid":false,"given":"Laia","family":"Montoliu-Gaya","sequence":"first","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 41 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Strydom","sequence":"additional","affiliation":[{"name":"Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King\u2019s College London, London WC2R 2LS, UK"},{"name":"South London and Maudsley NHS Foundation Trust, London SE5 8AZ, UK"},{"name":"London Down Syndrome Consortium (LonDowns), London, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 41 M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 413 45 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 41 M\u00f6lndal, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 413 45 M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, Queen Square Institute of Neurology, University College London, London WC1N 3BG, UK"},{"name":"UK Dementia Research Institute, University College London, London WC1E 6BT, UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases, Hong Kong, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3579-8804","authenticated-orcid":false,"given":"Nicholas James","family":"Ashton","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, The Sahlgrenska Academy at the University of Gothenburg, 431 41 M\u00f6lndal, Sweden"},{"name":"Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Gothenburg, Sweden"},{"name":"Department of Old Age Psychiatry, Maurice Wohl Clinical Neuroscience Institute, King\u2019s College London, London SE5 9RT, UK"},{"name":"NIHR Biomedical Research Centre for Mental Health, Biomedical Research Unit for Dementia at South London, Maudsley NHS Foundation, London SE5 8AF, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1354","DOI":"10.1016\/S0140-6736(88)90881-1","article-title":"Life expectancy in Down syndrome adults","volume":"2","author":"Baird","year":"1988","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1001\/jamaneurol.2018.3443","article-title":"Prevalence and Severity of Alzheimer Disease in Individuals with Down Syndrome","volume":"76","author":"Rafii","year":"2019","journal-title":"JAMA Neurol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"622","DOI":"10.1016\/S1474-4422(16)00063-6","article-title":"Dementia in Down\u2019s syndrome","volume":"15","author":"Ballard","year":"2016","journal-title":"Lancet Neurol."},{"key":"ref_4","first-page":"1","article-title":"Cerebrospinal fluid biomarkers for Alzheimer\u2019s disease in Down syndrome","volume":"8","author":"Dekker","year":"2017","journal-title":"Alzheimers Dement."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1006\/nbdi.1996.0003","article-title":"Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: Implications for initial events in amyloid plaque formation","volume":"3","author":"Lemere","year":"1996","journal-title":"Neurobiol. 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