Association of the MAOB rs1799836 Single Nucleotide Polymorphism and APOE ε4 Allele in Alzheimer’s Disease

Scientific paper - Original scientific paper

• Author: Mirjana Babić Leko
• Author: Matea Nikolac Perković
• Author: Gordana Nedić Erjavec
• 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 Anatomy and Clinical Anatomy)
• Author's institution: University of Zagreb; School of Medicine; (Department of Neurology)
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Anatomy
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Neurology
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Neuroscience

Abstract (english)

Background: The dopaminergic system is functionally compromised in Alzheimer's Disease (AD). The activity of Monoamine Oxidase B (MAOB), the enzyme involved in the degradation of dopamine, is increased during AD. Also, increased expression of MAOB occurs in the postmortem hippocampus and neocortex of patients with AD. The MAOB rs1799836 polymorphism modulates MAOB transcription, consequently influencing protein translation and MAOB activity. We recently showed that cerebrospinal fluid levels of amyloid β1-42 are decreased in patients carrying the A allele in MAOB rs1799836 polymorphism.
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Objective: The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD.
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Methods: We included 253 participants, 127 of whom had AD, 57 had mild cognitive impairment, 11 were healthy controls, and 58 suffered from other primary causes of dementia. MAOB and APOE polymorphisms were determined using TaqMan SNP Genotyping Assays.
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Results: We observed that the frequency of APOE ε4/ε4 homozygotes and APOE ε4 carriers is significantly increased among patients carrying the AA MAOB rs1799836 genotype.
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Conclusion: These results indicate that the MAOB rs1799836 polymorphism is a potential genetic biomarker of AD and a potential target for the treatment of decreased dopaminergic transmission and cognitive deterioration in AD.

• Keywords (english): Alleles; Alzheimer Disease / genetics; Apolipoprotein E4 / genetics; Genotype; Humans; Monoamine Oxidase / genetics; Polymorphism, Single Nucleotide
• Language: english
• Publication type: Scientific paper - Original scientific paper
• Publication status: Published
• Peer review: Peer review
• Publication version: Published version
• Journal title: Current Alzheimer Research
• Numbering: vol. 18, no. 7, pp. 585-594
• p-ISSN: 1567-2050
• e-ISSN: 1875-5828
• DOI: https://doi.org/10.2174/1567205018666210917162843
• URN:NBN: urn:nbn:hr:105:989394
• Publication: 2021-06
• Project: Number: IP-2019-04-3584; Title (croatian): Uloga krvno-moždane barijere, urođene imunosti i oligomerizacije tau proteina u patogenezi Alzheimerove bolesti; Title (english): Role of blood-brain barrier, innate immunity, and tau protein oligomerization in the pathogenesis of Alzheimer's disease; Acronym: ALZ-BBB-INNATETAU; Leader: Goran Šimić; Jurisdiction: Croatia; Funding stream: IP
• Document URL: https://www.eurekaselect.com/196621/article
• Type of resource: Text
• Access conditions: Open access; Embargo expiration date: 2022-07-01
• Created on: 2022-04-28 10:47:51