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

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• Autor: Mirjana Babić Leko
• Autor: Matea Nikolac Perković
• Autor: Nataša Klepac
• Autor: Dubravka Švob Štrac
• Autor: Fran Borovečki
• Autor: Nela Pivac
• Autor: Patrick R. Hof
• Autor: Goran Šimić
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (HRVATSKI INSTITUT ZA ISTRAŽIVANJE MOZGA)
• Autorova ustanova: Sveučilište u Zagrebu; Medicinski fakultet; (KATEDRA ZA NEUROLOGIJU)
• Znanstveno / umjetničko područje, polje i grana: BIOMEDICINA I ZDRAVSTVO; Kliničke medicinske znanosti; Neurologija

Sažetak (engleski)

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.

• Ključne riječi (engleski): Alzheimer’s disease; biomarkers; COMT; DBH; dopamine; MAOB; noradrenaline; polymorphisms
• Jezik: engleski
• Vrsta publikacije: Znanstveni rad - Izvorni znanstveni rad
• Status objave: Objavljen
• Vrsta recenzije: Recenziran
• Verzija publikacije: Objavljena verzija rada (izdavačev PDF)
• Naslov časopisa: Journal of Alzheimer's Disease
• Brojčani podaci: vol. 73, br. 1, str. 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
• Datum objave publikacije: 2020-01-07
• URL dokumenta: https://www.medra.org/servlet/aliasResolver?alias=iospress&doi=10.3233/JAD-190991
• Vrsta resursa: Tekst
• Prava pristupa: Otvoreni pristup
• Datum i vrijeme pohrane: 2020-10-26 09:53:49