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Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort
INTRODUCTION: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporad...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236251/ https://www.ncbi.nlm.nih.gov/pubmed/30329219 http://dx.doi.org/10.1002/brb3.1128 |
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author | Babić Leko, Mirjana Willumsen, Nanet Nikolac Perković, Matea Klepac, Nataša Borovečki, Fran Hof, Patrick R. Sonicki, Zdenko Pivac, Nela de Silva, Rohan Šimić, Goran |
author_facet | Babić Leko, Mirjana Willumsen, Nanet Nikolac Perković, Matea Klepac, Nataša Borovečki, Fran Hof, Patrick R. Sonicki, Zdenko Pivac, Nela de Silva, Rohan Šimić, Goran |
author_sort | Babić Leko, Mirjana |
collection | PubMed |
description | INTRODUCTION: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two ε4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule‐associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. METHODS: The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype‐tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del–In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid β(1–42) (Aβ(1–42)), total tau (t‐tau), tau phosphorylated at epitopes 181 (p‐tau(181)), 199 (p‐tau(199)), and 231 (p‐tau(231)), and visinin‐like protein 1 (VILIP‐1). RESULTS: Significant increases in t‐tau and p‐tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. CONCLUSIONS: These results indicate that MAPT haplotype‐tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD. |
format | Online Article Text |
id | pubmed-6236251 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62362512018-11-20 Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort Babić Leko, Mirjana Willumsen, Nanet Nikolac Perković, Matea Klepac, Nataša Borovečki, Fran Hof, Patrick R. Sonicki, Zdenko Pivac, Nela de Silva, Rohan Šimić, Goran Brain Behav Original Research INTRODUCTION: Alzheimer's disease (AD) is the world leading cause of dementia. Early detection of AD is essential for faster and more efficacious usage of therapeutics and preventive measures. Even though it is well known that one ε4 allele of apolipoprotein E gene increases the risk for sporadic AD five times, and that two ε4 alleles increase the risk 20 times, reliable genetic markers for AD are not yet available. Previous studies have shown that microtubule‐associated protein tau (MAPT) gene polymorphisms could be associated with increased risk for AD. METHODS: The present study included 113 AD patients and 53 patients with mild cognitive impairment (MCI), as well as nine healthy controls (HC) and 53 patients with other primary causes of dementia. The study assessed whether six MAPT haplotype‐tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del–In9, and rs7521) and MAPT haplotypes are associated with AD pathology, as measured by cerebrospinal fluid (CSF) AD biomarkers amyloid β(1–42) (Aβ(1–42)), total tau (t‐tau), tau phosphorylated at epitopes 181 (p‐tau(181)), 199 (p‐tau(199)), and 231 (p‐tau(231)), and visinin‐like protein 1 (VILIP‐1). RESULTS: Significant increases in t‐tau and p‐tau CSF levels were found in patients with AG and AA MAPT rs1467967 genotype, CC MAPT rs2471738 genotype and in patients with H1H2 or H2H2 MAPT haplotype. CONCLUSIONS: These results indicate that MAPT haplotype‐tagging polymorphisms and MAPT haplotypes should be further tested as potential genetic biomarkers of AD. John Wiley and Sons Inc. 2018-10-17 /pmc/articles/PMC6236251/ /pubmed/30329219 http://dx.doi.org/10.1002/brb3.1128 Text en © 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Babić Leko, Mirjana Willumsen, Nanet Nikolac Perković, Matea Klepac, Nataša Borovečki, Fran Hof, Patrick R. Sonicki, Zdenko Pivac, Nela de Silva, Rohan Šimić, Goran Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title | Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title_full | Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title_fullStr | Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title_full_unstemmed | Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title_short | Association of MAPT haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of Alzheimer's disease: A preliminary study in a Croatian cohort |
title_sort | association of mapt haplotype‐tagging polymorphisms with cerebrospinal fluid biomarkers of alzheimer's disease: a preliminary study in a croatian cohort |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6236251/ https://www.ncbi.nlm.nih.gov/pubmed/30329219 http://dx.doi.org/10.1002/brb3.1128 |
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