Relationships of Cerebrospinal Fluid Alzheimer's Disease Biomarkers and COMT, DBH, and MAOB Single Nucleotide Polymorphisms.
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 β-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-β42 (Aβ42), 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 Aβ42 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. Aβ42 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.
['Babić Leko|Mirjana|M|', 'Nikolac Perković|Matea|M|', 'Klepac|Nataša|N|', 'Švob Štrac|Dubravka|D|', 'Borovečki|Fran|F|', 'Pivac|Nela|N|', 'Hof|Patrick R|PR|', 'Šimić|Goran|G|']
D000368:Aged D000544:Alzheimer Disease D002394:Catechol O-Methyltransferase D060825:Cognitive Dysfunction D017523:Croatia D004247:DNA D004299:Dopamine beta-Hydroxylase D005260:Female D005787:Gene Frequency D005838:Genotype D006579:Heterozygote D006801:Humans D008297:Male D008875:Middle Aged D008995:Monoamine Oxidase D020641:Polymorphism, Single Nucleotide D016875:tau Proteins
biomarkers COMT DBH MAOB polymorphisms dopamine noradrenaline Alzheimer’s disease