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

[ Vol. 18 , Issue. 7 ]

Author(s):

Mirjana B. Leko, Matea N. Perković, Gordana N. Erjavec, Nataša Klepac, Dubravka Š. Štrac, Fran Borovečki, Nela Pivac, Patrick R. Hof and Goran Šimić*   Pages 585 - 594 ( 10 )

Abstract:


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.

Objective: The present study compares MAOB rs1799836 polymorphism and APOE, the only confirmed genetic risk factor for sporadic AD.

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.

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.

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:

Alzheimer's disease, MAOB, APOE, polymorphisms, genetic biomarkers, mild cognitive impairment.

Affiliation:

Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb, Department of Molecular Medicine, Institute Ruder Boskovic, Zagreb, Department of Molecular Medicine, Institute Ruder Boskovic, Zagreb, Department of Neurology, University Hospital Centre Zagreb, Zagreb, Department of Molecular Medicine, Institute Ruder Boskovic, Zagreb, Department of Neurology, University Hospital Centre Zagreb, Zagreb, Department of Molecular Medicine, Institute Ruder Boskovic, Zagreb, Nash Family Department of Neuroscience, Friedman Brain Institute, and Ronald M. Loeb Center for Alzheimer’s Disease, Icahn School of Medicine at Mount Sinai, New York, NY 10029, Department of Neuroscience, Croatian Institute for Brain Research, University of Zagreb Medical School, Zagreb



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