Skip to main content

ORIGINAL RESEARCH article

Front. Mol. Neurosci.
Sec. Brain Disease Mechanisms
Volume 17 - 2024 | doi: 10.3389/fnmol.2024.1456670
This article is part of the Research Topic Latest Advances in Neuroscience at the 9th Croatian Neuroscience Congress View all 8 articles

Further validation of the association between MAPT haplotype-tagging polymorphisms and Alzheimer's disease: neuropsychological tests, cerebrospinal fluid biomarkers, and APOE genotype

Provisionally accepted
Mirjana Babić Leko Mirjana Babić Leko 1*Ena Španić Popovački Ena Španić Popovački 1Nanet Willumsen Nanet Willumsen 2Matea Nikolac Perković Matea Nikolac Perković 3Nikolina Pleić Nikolina Pleić 4Klara Zubčić Klara Zubčić 5Lea Langer Horvat Lea Langer Horvat 1Željka Vogrinc Željka Vogrinc 6Marina Boban Marina Boban 7,8Fran Borovečki Fran Borovečki 7,8,9Tatijana Zemunik Tatijana Zemunik 10,4Rohan de Silva Rohan de Silva 2Goran Šimić Goran Šimić 1*
  • 1 Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia, Zagreb, Croatia
  • 2 Reta Lila Weston Institute and Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK, London, United Kingdom
  • 3 Ruđer Bošković Institute, Division of Molecular Medicine, Zagreb, Croatia, Zagreb, Croatia
  • 4 Department of Biology and Human Genetics, School of Medicine, University of Split, Split, Croatia, Split, Croatia
  • 5 Department of Molecular Diagnostics and Genetics, Dubrava University Hospital, Zagreb, Croatia, Zagreb, Croatia
  • 6 Laboratory for Neurobiochemistry, Department of Laboratory Diagnostics, University Hospital Centre Zagreb, Zagreb, Croatia, Zagreb, Croatia
  • 7 Department of Neurology, University Hospital Centre Zagreb, Kišpatićeva 12, 10000 Zagreb, Croatia, Zagreb, Croatia
  • 8 School of Medicine, University of Zagreb, Zagreb, Croatia
  • 9 Department for Functional Genomics, Center for Translational and Clinical Research, University of Zagreb Medical School, Zagreb, Croatia, Zagreb, Croatia
  • 10 Department of Nuclear Medicine, University Hospital Split, Split, Croatia, Split, Croatia

The final, formatted version of the article will be published soon.

    Genetic studies have shown that variants in the microtubule-associated protein tau (MAPT) gene, which encodes tau protein, can increase the risk for Alzheimer's disease (AD).Additionally, two haplotypes in the MAPT gene (H1 and H2) are associated with various neurodegenerative disorders, including AD. This study aimed to test the association of MAPT haplotypes (H1 and H2) and MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883,rs2471738,rs7521) with AD. The study included 964 individuals: 113 with AD, 53 with mild cognitive impairment (MCI), 54 with other dementias, and 744 healthy controls. The results showed that individuals carrying the A allele in the MAPT rs1467967 polymorphism, the GG genotype in the MAPT rs7521 polymorphism, and the G allele in the MAPT rs242557 polymorphism had worse performance on various neuropsychological tests. Carriers of the C allele in MAPT rs2471738 polymorphism and CC homozygotes also showed worse performance on neuropsychological tests and pathological levels of several cerebrospinal fluid (CSF) biomarkers. However, T allele carriers in the MAPT rs2471738 polymorphism were more represented among patients with dementia and apolipoprotein E (APOE) ɛ4 carriers. Carriers of the H2 MAPT haplotype had worse performance on various neuropsychological tests, consistent with our previous study, which associated the H2 MAPT haplotype with pathological levels of CSF AD biomarkers. Regarding the MAPT rs3785883 polymorphism, further research is needed since both the AA and GG genotypes were associated with CSF and plasma AD biomarkers. Therefore, further genetic studies are needed to elucidate the role of MAPT haplotypes and MAPT haplotype-tagging polymorphisms in the development of AD.

    Keywords: Alzheimer's disease, APOE gene, biomarkers, Cerebrospinal Fluid, Dementia, MAPT gene, MAPT haplotypes, MAPT polymorphisms

    Received: 01 Jul 2024; Accepted: 28 Aug 2024.

    Copyright: © 2024 Babić Leko, Španić Popovački, Willumsen, Nikolac Perković, Pleić, Zubčić, Langer Horvat, Vogrinc, Boban, Borovečki, Zemunik, de Silva and Šimić. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Mirjana Babić Leko, Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia, Zagreb, Croatia
    Goran Šimić, Department for Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Croatia, Zagreb, Croatia

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.