Genotype-independent decrease in plasma dopamine beta-hydroxylase activity in Alzheimer's disease

Mustapić, Maja and Presečki, Paola and Pivac, Nela and Mimica, Ninoslav and Hof, Patrick R. and Šimić, Goran and Folnegović-Šmalc, Vera and Muck-Šeler, Dorotea (2013) Genotype-independent decrease in plasma dopamine beta-hydroxylase activity in Alzheimer's disease. Progress in Neuro-Psychopharmacology and Biological Psychiatry, 44. pp. 94-9. ISSN 0278-5846

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Abstract

The noradrenergic system is involved in the etiology and progression of Alzheimer's disease (AD) but its role is still unclear. Dopamine beta-hydroxylase (DBH) as a catecholamine-synthesizing enzyme plays a central role in noradrenaline (NA) synthesis and turnover. Plasma DBH (pDBH) activity shows wide inheritable interindividual variability that is under genetic control. The aim of this study was to determine pDBH activity, DBH (C-970T; rs1611115) and DBH (C1603T; rs6271) gene polymorphisms in 207 patients with AD and in 90 healthy age-matched controls. Plasma DBH activity was lower, particularly in the early stage of AD, compared to values in middle and late stages of the disease, as well as to control values. Two-way ANOVA revealed significant effect of both diagnosis and DBH (C-970T) or DBH (C1603T) genotypes on pDBH activity, but without significant diagnosis×genotype interaction. No association was found between AD and DBH C-970T (OR=1.08, 95% CI 1.13-4.37; p=0.779) and C1603T (OR=0.89; 95% CI 0.36-2.20; p=0.814) genotypes controlled for age, gender, and ApoE4 allele. The decrease in pDBH activity, found in early phase of AD suggests that alterations in DBH activity represent a compensatory mechanism for the loss of noradrenergic neurons, and that treatment with selective NA reuptake inhibitors may be indicated in early stages of AD to compensate for loss of noradrenergic activity in the locus coeruleus.

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