Relationships of Cerebrospinal Fluid Alzheimer’s Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms

Scientific paper - Original scientific paper

• Author: Mirjana Babić Leko
• Author: Matea Nikolac Perković
• Author: Nataša Klepac
• Author: Dubravka Švob Štrac
• Author: Fran Borovečki
• Author: Nela Pivac
• Author: Patrick R. Hof
• Author: Goran Šimić
• Author's institution: University of Zagreb; School of Medicine; (Croatian Institiute for Brain Research)
• Author's institution: University of Zagreb; School of Medicine; (Department of Neurology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology

Abstract (english)

The noradrenergic and dopaminergic systems are affected in Alzheimer’s disease (AD). Polymorphisms in genes
encoding enzymes and proteins that are components of these systems can affect products of transcription and translation and
lead to altered enzymatic activity and alterations in overall dopamine and noradrenaline levels. Catechol-O-methyltransferase
(COMT) and monoamine oxidase B (MAOB) are the enzymes that regulate degradation of dopamine, while dopamine -
hydroxylase (DBH) is involved in synthesis of noradrenaline. COMT Val158Met (rs4680), DBH rs1611115 (also called
–1021C/T or –970C/T), and MAOB rs1799836 (also called A644G) polymorphisms have been previously associated with
AD. We assessed whether these polymorphisms are associated with cerebrospinal fluid (CSF) AD biomarkers including
total tau (t-tau), phosphorylated tau proteins (p-tau181, p-tau199, and p-tau231), amyloid-42 (A42), and visinin-like protein
1 (VILIP-1) to test possible relationships of specific genotypes and pathological levels of CSF AD biomarkers. The study
included 233 subjects: 115 AD, 53 mild cognitive impairment, 54 subjects with other primary causes of dementia, and 11
healthy controls. Significant decrease in A42 levels was found in patients with GG compared to AG COMT Val158Met
genotype, while t-tau and p-tau181 levels were increased in patients with AA compared to AG COMT Val158Met genotype.
A42 levels were also decreased in carriers of A allele in MAO-B rs1799836 polymorphism, while p-tau181 levels were
increased in carriers of T allele in DBH rs1611115 polymorphism. These results indicate that COMT Val158Met, DBH
rs1611115, and MAOB rs1799836 polymorphisms deserve further investigation as genetic markers of AD.

• Keywords (english): Alzheimer’s disease; biomarkers; COMT; DBH; dopamine; MAOB; noradrenaline; polymorphisms
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Journal of Alzheimer's Disease
• Numbering: vol. 73, no. 1, pp. 135-145
• p-ISSN: 1387-2877
• e-ISSN: 1875-8908
• DOI: https://doi.org/10.3233/JAD-190991
• URN:NBN: urn:nbn:hr:105:926875
• Publication: 2020-01-07
• Document URL: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-190991
• Type of resource: Text
• Access conditions: Open access
• Created on: 2020-10-26 09:53:49