Increased Lymphocyte Dopamine β-Hydroxylase Immunoreactivity in Alzheimer’s Disease: Compensatory Response to Cholinergic Deficit?

Abstract

There is growing interest in the characterization of peripheral blood lymphocytes (PBL) as a biological tool with which to investigate changes in the neurotransmitter-receptor system in neurodegenerative disorders. Here we show a slight decrease in acetylcholinesterase (AChE) and a significant increase in dopamine β-hydroxylase (DBH) immunoreactivity in the PBL of patients with probable Alzheimer’s disease (AD). Therapy with AChE inhibitors completely reversed the increase in DBH immunoreactivity. We hypothesize that the increase in DBH immunoreactivity may represent a compensatory response to cholinergic impairment. Our findings suggest that neurochemical interactions between the noradrenergic and cholinergic systems may be measured at a peripheral level in AD.

Quantitative Serum Proteomics of Tryptophan Nutrition Using Bi-directional Heavy Oxygen Labeling with a RuBisCO Internal Standard

“…Dopamine beta-hydroxylase (DBH), responsible for conversion of dopamine to norepinephrine, was increased and supports previous work showing that excess dietary tryptophan decreases norepinephrine in blood plasma [44]. DBH also blocks selective serotonin reuptake inhibitors (SSRI) thus decreasing the concentration of serotonin, a tryptophan derivative, in the hippocampus [45]. PPARBP was also increased.…”

“…A flow rate of L/min was used for both SCX and RP columns. A salt gradient was applied in steps of 0, 10,15,20,25,30,35,40,45,50,57,64,90 and 700 mM ammonium acetate in 5% ACN, 0.1% formic acid and the resultant peptides loaded directly into the sample loop of a 0.18 x 100 mm BioBasic C18 RP LC column of a ProteomeX workstation (Thermo Electron). The RP gradient used 0.1% formic acid in ACN and increased the ACN concentration in a linear gradient from 5% to 30% in 30 min and then 30% to 65% in 9 min followed by 95% for 5 min and 5% for 15 min.…”

Noradrenergic dysfunction in Alzheimer's disease

“…Tyrosine hydroxylase, which catalyzes the rate-limiting step in the production of norepinephrine, is increased in the brain of AD patients (Iversen et al, 1983; Szot et al, 2006, 2007). The enzyme DβH is also increased in serum, CSF, and peripheral blood lymphocytes in AD cases (Miyata et al, 1984; Giubilei et al, 2004). …”

Nerve Driven Immunity: Noradrenaline and Adrenaline

“…2.1) for the synthesis of noradrenaline and adrenaline in immune cells is suggested by the expression of the enzyme tyrosine hydroxylase (TH, EC 1.14.16.2), the first and rate-limiting enzyme in the synthesis of catecholamines, which undergoes upregulation following cell stimulation, as well as by the ability of the TH inhibitor a-methyl-p-tyrosine, the RNApolymerase inhibitor actinomycin D and the protein synthesis inhibitor cycloheximide to prevent intracellular enhancement of catecholamine levels (Cosentino Reguzzoni et al 2002). Only fragmentary evidence however exists regarding the expression and activity in immune cells of other key enzymes such as phenylethanolamine N-methyltransferase (Andreassi et al 1998;Ziegler et al 2002) or dopamine b-hydroxylase (Giubilei et al 2004).…”