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Stiftelse, Stockholm, Sweden","award":["#ALZ2022-0006"],"award-info":[{"award-number":["#ALZ2022-0006"]}]},{"name":"Familjen R\u00f6nstr\u00f6ms Stiftelse, Stockholm, Sweden","award":["#ALFGBG-715986"],"award-info":[{"award-number":["#ALFGBG-715986"]}]},{"name":"Familjen R\u00f6nstr\u00f6ms Stiftelse, Stockholm, Sweden","award":["#ALFGBG-965240"],"award-info":[{"award-number":["#ALFGBG-965240"]}]},{"name":"Familjen R\u00f6nstr\u00f6ms Stiftelse, Stockholm, Sweden","award":["JPND2019-466-236"],"award-info":[{"award-number":["JPND2019-466-236"]}]},{"name":"Familjen R\u00f6nstr\u00f6ms Stiftelse, Stockholm, Sweden","award":["ZEN-21-848495"],"award-info":[{"award-number":["ZEN-21-848495"]}]},{"name":"Familjen R\u00f6nstr\u00f6ms Stiftelse, Stockholm, Sweden","award":["SG-23-1038904 QC"],"award-info":[{"award-number":["SG-23-1038904 QC"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: SERPINE1, also known as plasminogen activator inhibitor (PAI), has been proposed as a potential blood biomarker for the early detection and diagnosis of Alzheimer\u2019s disease (AD). Expanding on previous studies, this research contrasted SERPINE1 levels in CSF and brain tissue of AD patients and those at risk for AD with established AD biomarkers. Methods: Utilizing OLINK and immunoassay methods, CSF SERPINE1 protein levels were quantified across two separate cohorts: PREVENT-AD and ADNI. Microarray and RNAseq were used to measure tissue SERPINE1 mRNA levels in two separate cohorts: the Douglas-Bell Canada Brain Bank and the Mayo Clinic Brain Bank. Results: At the pre-clinical stage, elevated CSF levels of pTau, tTau and synaptic markers, alongside reduced hippocampal volume, correlate with CSF SERPINE1 levels. Elevated cortical SERPINE1 mRNA levels in autopsy-confirmed AD show weak correlation with regional plaques and tangles densities, but strong correlation with Braak staging. Conclusions: CSF SERPINE1 levels can be used as an early biomarker for the detection of pathological changes associated with AD. Higher SERPINE1 levels correlate more strongly with tau pathology than with amyloid formation or deposition.<\/jats:p>","DOI":"10.3390\/genes16070818","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T10:46:05Z","timestamp":1752662765000},"page":"818","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Brain and CSF Alzheimer\u2019s Biomarkers Are Associated with SERPINE1 Gene Expression"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1107-6839","authenticated-orcid":false,"given":"Cynthia","family":"Picard","sequence":"first","affiliation":[{"name":"Douglas Mental Health University Institute, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Centre for the Studies on Prevention of Alzheimer\u2019s Disease, Montr\u00e9al, QC H4H 1R3, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henrik","family":"Zetterberg","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 30 M\u00f6lndal, Sweden"},{"name":"Department of Neurodegenerative Disease, UCL Institute of Neurology, London WC1N 3BG, UK"},{"name":"UK Dementia Research Institute at UCL, London WC1E 6BT, UK"},{"name":"Hong Kong Center for Neurodegenerative Diseases, Hong Kong 1501-02 15, China"},{"name":"Wisconsin Alzheimer\u2019s Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI 53715, USA"},{"name":"Centre for Brain Research, Indian Institute of Science, Bangladore 560012, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaj","family":"Blennow","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy, University of Gothenburg, SE-405 30 Gothenburg, Sweden"},{"name":"Clinical Neurochemistry Laboratory, Sahlgrenska University Hospital, 431 30 M\u00f6lndal, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Villeneuve","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Centre for the Studies on Prevention of Alzheimer\u2019s Disease, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Department of Psychiatry, McGill University, Montr\u00e9al, QC H3A 0C8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8018-4545","authenticated-orcid":false,"given":"Judes","family":"Poirier","sequence":"additional","affiliation":[{"name":"Douglas Mental Health University Institute, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Centre for the Studies on Prevention of Alzheimer\u2019s Disease, Montr\u00e9al, QC H4H 1R3, Canada"},{"name":"Department of Psychiatry, McGill University, Montr\u00e9al, QC H3A 0C8, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the PREVENT-AD Research Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1111\/j.1755-5922.2010.00171.x","article-title":"Plasminogen activator inhibitor-1 (PAI-1): A key factor linking fibrinolysis and age-related subclinical and clinical conditions","volume":"28","author":"Cesari","year":"2010","journal-title":"Cardiovasc. 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