{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T17:18:31Z","timestamp":1777396711455,"version":"3.51.4"},"reference-count":71,"publisher":"SAGE Publications","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JAD"],"published-print":{"date-parts":[[2020,11,10]]},"abstract":"<jats:p>Background: Mild cognitive impairment (MCI) has been considered as a pre-dementia stage, although the factors leading to Alzheimer\u2019s disease (AD) conversion remain controversial. Objective: Evaluate whether TOMM40 poly-T (TOMM40\u2032 523) polymorphism is associated with the risk and conversion time from MCI to AD and secondly with AD cerebrospinal fluid (CSF) biomarkers, disentangling the APOE genotype. Methods: 147 AD patients, 102 MCI patients, and 105 cognitively normal controls were genotyped for poly-T polymorphism. MCI patients were subdivided into two groups, the group of patients that converted to AD (MCI-AD) and the group of those that remained stable (MCI-S). Results: TOMM40\u2032 523 L allele was significantly more frequent in the MCI-AD group and having at least one L allele significantly increased the risk of conversion from MCI to AD (OR\u200a=\u200a8.346, p\u200a&lt;\u200a0.001, 95% CI: 2.830 to 24.617). However, when adjusted for the presence of APOE \u025b4 allele, both the L allele and \u025b4 allele lost significance in the model (p\u200a&gt;\u200a0.05). We then analyzed the APOE \u025b4-TOMM40\u2032 523 L haplotype and observed that patients carrying this haplotype had significantly higher risk (OR\u200a=\u200a5.83; 95% CI\u200a=\u200a2.30\u201314.83) and mean lower times of conversion to AD (p\u200a=\u200a0.003). This haplotype was also significantly associated with a biomarker profile compatible with AD (p\u200a=\u200a0.007). Conclusion: This study shows that the APOE \u025b4-TOMM40\u2032 523 L haplotype is associated with a higher risk and shorter times of conversion from MCI to AD, possibly driven by CSF biomarkers and mitochondrial dysfunction.<\/jats:p>","DOI":"10.3233\/jad-200556","type":"journal-article","created":{"date-parts":[[2020,9,29]],"date-time":"2020-09-29T16:05:08Z","timestamp":1601395508000},"page":"587-601","source":"Crossref","is-referenced-by-count":6,"title":["APOE \u025b4-TOMM40L Haplotype Increases the Risk of Mild Cognitive Impairment Conversion to Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"78","author":[{"given":"Remy","family":"Cardoso","sequence":"first","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"}]},{"given":"Carolina","family":"Lemos","sequence":"additional","affiliation":[{"name":"UnIGENe, IBMC \u2013Institute for Molecular and Cell Biology, Porto, Portugal"},{"name":"i3S \u2013Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade, Universidade do Porto, Porto, Portugal"},{"name":"ICBAS - Instituto Ci\u00eancias Biom\u00e9dicas Abel Salazar, Universidade do Porto, Porto, Portugal"}]},{"given":"B\u00e1rbara","family":"Oliveiros","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, University of Coimbra, Coimbra, Portugal"},{"name":"Laboratory of Biostatistics and Medical Informatics, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"},{"name":"Coimbra Institute for Clinical and Biomedical Research, Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Maria Ros\u00e1rio","family":"Almeida","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"}]},{"given":"In\u00eas","family":"Baldeiras","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Coimbra, Portugal"},{"name":"Neurochemistry Laboratory, Neurology Department, Coimbra University Hospital (CHUC), Coimbra, Portugal"}]},{"given":"Cl\u00e1udia Frag\u00e3o","family":"Pereira","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Coimbra, Portugal"}]},{"given":"Ana","family":"Santos","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"}]},{"given":"Diana","family":"Duro","sequence":"additional","affiliation":[{"name":"Neurology Department, Coimbra University Hospital (CHUC), Coimbra, Portugal"}]},{"given":"Daniela","family":"Vieira","sequence":"additional","affiliation":[{"name":"Neurology Department, Coimbra University Hospital (CHUC), Coimbra, Portugal"}]},{"given":"Isabel","family":"Santana","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Coimbra, Portugal"},{"name":"Neurology Department, Coimbra University Hospital (CHUC), Coimbra, Portugal"}]},{"given":"Catarina Resende","family":"Oliveira","sequence":"additional","affiliation":[{"name":"Center for Neuroscience and Cell Biology, CNC-CIBB, University of Coimbra, Coimbra, Portugal"},{"name":"Faculty of Medicine, University of Coimbra, Coimbra, Portugal"},{"name":"Clinical Academic Center of Coimbra, Coimbra, Portugal"}]}],"member":"179","reference":[{"key":"10.3233\/JAD-200556_ref1","doi-asserted-by":"crossref","first-page":"2227","DOI":"10.1056\/NEJMcp0910237","article-title":"Mild cognitive impairment","volume":"364","author":"Petersen","year":"2011","journal-title":"N Engl J 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