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 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.