TY - JOUR
T1 - Genotype-independent decrease in plasma dopamine beta-hydroxylase activity in Alzheimer's disease
AU - Mustapic, Maja
AU - Presecki, Paola
AU - Pivac, Nela
AU - Mimica, Ninoslav
AU - Hof, Patrick R.
AU - Simic, Goran
AU - Folnegovic-Smalc, Vera
AU - Muck-Seler, Dorotea
N1 - Funding Information:
The study was supported by Croatian Ministry of Science, Education and Sports (grant nos. 098-0982522-2457 , 098-0982522-2455 and 108-1081870-2418 ), Croatian Science Foundation grant no. 09/16 , as well as COST Action CM1103 . Thanks are due to the staff of University Psychiatric Hospital Vrapce and Psychiatric Hospital Sv. Ivan, Zagreb, Croatia.
PY - 2013/7/1
Y1 - 2013/7/1
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - Cognitive decline
KW - DBH gene polymorphisms
KW - Dopamine beta-hydroxylase
KW - Plasma DBH activity
UR - https://www.scopus.com/pages/publications/84874523754
U2 - 10.1016/j.pnpbp.2013.02.002
DO - 10.1016/j.pnpbp.2013.02.002
M3 - Article
C2 - 23416088
AN - SCOPUS:84874523754
SN - 0278-5846
VL - 44
SP - 94
EP - 99
JO - Progress in Neuro-Psychopharmacology and Biological Psychiatry
JF - Progress in Neuro-Psychopharmacology and Biological Psychiatry
ER -