Dopamine turnover increases in asymptomatic LRRK2 mutations carriers.
Identifieur interne : 001515 ( PubMed/Corpus ); précédent : 001514; suivant : 001516Dopamine turnover increases in asymptomatic LRRK2 mutations carriers.
Auteurs : Vesna Sossi ; Raul De La Fuente-Fernández ; Ramachandiran Nandhagopal ; Michael Schulzer ; Jessamyn Mckenzie ; Thomas J. Ruth ; Jan O. Aasly ; Matthew J. Farrer ; Zbigniew K. Wszolek ; Jon A. StoesslSource :
- Movement disorders : official journal of the Movement Disorder Society [ 1531-8257 ] ; 2010.
English descriptors
- KwdEn :
- Adult, Aged, Brain (metabolism), Brain (radionuclide imaging), Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (metabolism), Female, Genotype, Humans, Male, Middle Aged, Mutation, Protein-Serine-Threonine Kinases (genetics), Protein-Serine-Threonine Kinases (metabolism), Statistics, Nonparametric.
- MESH :
- chemical , genetics : Protein-Serine-Threonine Kinases.
- chemical , metabolism : Dopamine, Dopamine Plasma Membrane Transport Proteins, Protein-Serine-Threonine Kinases.
- metabolism : Brain.
- radionuclide imaging : Brain.
- Adult, Aged, Female, Genotype, Humans, Male, Middle Aged, Mutation, Statistics, Nonparametric.
Abstract
Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: ¹⁸F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K(occ), a marker of DA synthesis and storage; ¹¹C-methylphenidate (MP, a DAT marker) and ¹¹C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP(ND_MP) and BP(ND_DTBZ). On average, EDV showed the largest reduction from age-matched control values (42%) followed by BP(ND_MP) (23%) and BP(ND_DTBZ) (17%), whereas K(occ) remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.
DOI: 10.1002/mds.23356
PubMed: 20939082
Links to Exploration step
pubmed:20939082Le document en format XML
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<author><name sortKey="Sossi, Vesna" sort="Sossi, Vesna" uniqKey="Sossi V" first="Vesna" last="Sossi">Vesna Sossi</name>
<affiliation><nlm:affiliation>Department of Physics and Astronomy, University of British Columbia, Vancouver British Columbia, Canada. vesna@phas.ubc.ca</nlm:affiliation>
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<author><name sortKey="De La Fuente Fernandez, Raul" sort="De La Fuente Fernandez, Raul" uniqKey="De La Fuente Fernandez R" first="Raul" last="De La Fuente-Fernández">Raul De La Fuente-Fernández</name>
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<author><name sortKey="Nandhagopal, Ramachandiran" sort="Nandhagopal, Ramachandiran" uniqKey="Nandhagopal R" first="Ramachandiran" last="Nandhagopal">Ramachandiran Nandhagopal</name>
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<author><name sortKey="Schulzer, Michael" sort="Schulzer, Michael" uniqKey="Schulzer M" first="Michael" last="Schulzer">Michael Schulzer</name>
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<author><name sortKey="Ruth, Thomas J" sort="Ruth, Thomas J" uniqKey="Ruth T" first="Thomas J" last="Ruth">Thomas J. Ruth</name>
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<term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term>
<term>Female</term>
<term>Genotype</term>
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<front><div type="abstract" xml:lang="en">Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: ¹⁸F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K(occ), a marker of DA synthesis and storage; ¹¹C-methylphenidate (MP, a DAT marker) and ¹¹C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP(ND_MP) and BP(ND_DTBZ). On average, EDV showed the largest reduction from age-matched control values (42%) followed by BP(ND_MP) (23%) and BP(ND_DTBZ) (17%), whereas K(occ) remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.</div>
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<Abstract><AbstractText>Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: ¹⁸F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K(occ), a marker of DA synthesis and storage; ¹¹C-methylphenidate (MP, a DAT marker) and ¹¹C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP(ND_MP) and BP(ND_DTBZ). On average, EDV showed the largest reduction from age-matched control values (42%) followed by BP(ND_MP) (23%) and BP(ND_DTBZ) (17%), whereas K(occ) remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT.</AbstractText>
<CopyrightInformation>© 2010 Movement Disorder Society.</CopyrightInformation>
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