engleski

Diagnostic potential of cerebrospinal fluid biomarkers in Alzheimer's disease combined with tau genotypes

Alzheimer's disease (AD) is the most common sporadic tauopathy. Although it is not caused by mutation in the microtubule-associated protein tau (MAPT) gene, previous studies showed that biomarkers of AD differ between patients with different MAPT genotypes. In this study, we tried to reveal whether the diagnostic potential of cerebrospinal fluid (CSF) biomarkers amyloid β1-42 (Aβ1-42), total tau (t-tau), tau phosphorylated at epitope 181 (p-tau181), epitope 199 (p-tau199), epitope 231 (p-tau231) and visinin-like protein 1 (VILIP-1) could be improved by MAPT haplotype-tagging polymorphisms (rs1467967, rs242557, rs3785883, rs2471738, del-In9, rs7521). First, we compared if levels of Aβ1-42, t-tau, p-tau181, p-tau199, p-tau231, and VILIP-1 differed between patients with different MAPT genotypes (rs1467967, rs242557, rs3785883, rs2471738, del-In9, rs7521). Second, we analyzed the distribution of MAPT haplotypes (H1 and H2 haplotypes and their sub-haplotypes) in Croatian population. Of the analyzed polymorphisms the del-In9 insertion-deletion in MAPT intron 9 defines the H1/H2 division caused by the inversion, while other single nucleotide polymorphisms (SNPs) define sub-haplotypes. The study was conducted on 113 AD and 53 mild cognitive impairment (MCI) patients, 9 healthy controls and 54 patients with other causes of dementia (14 with vascular dementia (VaD), 22 with frontotemporal dementia (FTD), 7 with dementia with Lewy bodies, 3 with AD + VaD, 1 with corticobasal syndrome (CBS), 2 with Parkinson disease (PD), 1 with epilepsy and 4 with unspecified dementia). Levels of t-tau were significantly higher in subjects with AG in comparison to GG rs1467967 tau genotype (when all patients were analyzed together). This observation was also confirmed in the combined group of AD, MCI patients and healthy controls. Differences in levels of CSF biomarkers between other MAPT genotypes (rs242557, rs3785883, rs2471738, del-In9, rs7521) were lost after Bonferroni correction for multiple comparisons. Additionally, we detected 23 H1 sub-haplotypes and 5 H2 sub-haplotypes in the Croatian population.

Alzheimer's disease ; biomarkers ; cerebrospinal fluid ; genetic predisposition to disease ; single-nucleotide polymorphism ; tau proteins ; tau haplotypes

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