{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T14:09:44Z","timestamp":1779199784327,"version":"3.51.4"},"reference-count":41,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T00:00:00Z","timestamp":1777248000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Late-onset Alzheimer\u2019s disease (LOAD) is a multifactorial neurodegenerative disorder involving the interaction of genetic and environmental factors. Dysregulation of the fibrinolytic system, particularly an increase in plasminogen activator inhibitor-1 (PAI-1) levels, may contribute to Alzheimer\u2019s pathology. Vitronectin (VTN) regulates fibrinolysis by stabilizing PAI-1. This study investigated the relationships between plasma PAI-1 activity and VTN, SERPINE1 (PAI-1), and APOE gene variants in nineteen LOAD patients (&gt;65 years) and ten cognitively normal age-matched control groups. Methods: Targeted next-generation sequencing was used to analyze the VTN, APOE, and SERPINE1 genes in 19 LOAD patients and ten controls. Additionally, plasma PAI-1 activity was measured in both groups. Results: Plasma PAI-1 activity was statistically significantly higher in LOAD patients compared to controls (p = 0.04). Targeted next-generation sequencing results showed that VTN 5\u2032-UTR variants (rs7212814, rs1555584131, rs71135830, and rs11437594) were found in all patients and observed in 20% of controls (p = 0.0001). The VTN rs704 variant was detected in 84% of patients and 29% of controls (p = 0.001). VTN 5\u2032-UTR variants showed Spearman correlation with PAI-1 activity (r = 1.0; p &lt; 0.0001). SERPINE1 3\u2032-UTR variants (rs11178, rs41423845) were found to be associated with the disease (p = 0.027; p = 0.0001). The APOE\u03b53\/\u03b54 genotype was present in 52.6% of patients and was not associated with PAI-1 activity. VTN variants showed an association with LOAD. Conclusions: These findings suggest that VTN variants may contribute to LOAD pathogenesis by affecting PAI-1 and leading to fibrinolytic system dysregulation.<\/jats:p>","DOI":"10.3390\/genes17050516","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:43:51Z","timestamp":1777448631000},"page":"516","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Association of VTN Genotype with Plasminogen Activator Inhibitor-1 Activity in Late-Onset Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"17","author":[{"given":"Deniz","family":"Agirbasli","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Cerrahpasa Faculty of Medicine, Istanbul University-Cerrahpasa, 34098 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet","family":"Agirbasli","sequence":"additional","affiliation":[{"name":"Department of Cardiology, School of Medicine, Istanbul Medeniyet University, Uskudar, 34700 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mehmet Emin","family":"Cakir","sequence":"additional","affiliation":[{"name":"Department of Neurology, Sancaktepe \u015eehit Prof. Dr. Ilhan Varank Training and Research Hospital, Sancaktepe, 34785 Istanbul, Turkey"},{"name":"Department of Neurology, Goztepe Training and Research Hospital, Istanbul Medeniyet University, Kadikoy, 34722 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5372-4780","authenticated-orcid":false,"given":"Meltem","family":"Muftuoglu","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics, Faculty of Engineering and Natural Sciences, Graduate School of Natural and Applied Sciences, Acibadem Mehmet Ali Aydinlar University, Atasehir, 34752 Istanbul, Turkey"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1159\/000490739","article-title":"Definition of Late Onset Alzheimer\u2019s Disease and Anticipation Effect of Genome-Wide Significant Risk Variants: Pilot Study of the APOE e4 Allele","volume":"77","author":"Spalletta","year":"2019","journal-title":"Neuropsychobiology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/s13024-019-0333-5","article-title":"The neuropathological diagnosis of Alzheimer\u2019s disease","volume":"14","author":"DeTure","year":"2019","journal-title":"Mol. 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