ParkinsonCanadaV1, Main, Exploration, bibRecord, 002385

Progression of dopaminergic dysfunction in a LRRK2 kindred : A multitracer PET study

Identifieur interne : 002385 ( Main/Exploration ); précédent : 002384; suivant : 002386

Progression of dopaminergic dysfunction in a LRRK2 kindred : A multitracer PET study

Auteurs : R. Nandhagopal [Canada] ; E. Mak [Canada] ; M. Schulzer [Canada] ; J. Mckenzie [Canada] ; S. Mccormick [Canada] ; V. Sossi [Canada] ; T. J. Ruth [Canada] ; A. Strongosky [États-Unis] ; M. J. Farrer [États-Unis] ; Z. K. Wszolek [États-Unis] ; A. J. Stoessl [Canada]

Source :

Neurology [ 0028-3878 ] ; 2008.

RBID : Pascal:09-0038426

Descripteurs français

Pascal (Inist)
- Pathologie du système nerveux, Trouble fonctionnel, Tomoscintigraphie, Tomographie par émission de positons.

English descriptors

KwdEn :
- Adult, Aged, Disease Progression, Dopamine (metabolism), Dopamine Plasma Membrane Transport Proteins (metabolism), Dysfunction, Emission tomography, Female, Follow-Up Studies, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Linear Models, Male, Middle Aged, Nervous system diseases, Parkinson Disease (diagnostic imaging), Parkinson Disease (genetics), Parkinson Disease (metabolism), Positron emission tomography, Positron-Emission Tomography (methods), Predictive Value of Tests, Protein-Serine-Threonine Kinases (genetics), Putamen (metabolism), Radiopharmaceuticals.
MESH :
- chemical , genetics : Protein-Serine-Threonine Kinases.
- chemical , metabolism : Dopamine, Dopamine Plasma Membrane Transport Proteins.
- diagnostic imaging : Parkinson Disease.
- genetics : Parkinson Disease.
- metabolism : Parkinson Disease, Putamen.
- methods : Positron-Emission Tomography.
- Adult, Aged, Disease Progression, Female, Follow-Up Studies, Humans, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, Linear Models, Male, Middle Aged, Predictive Value of Tests, Radiopharmaceuticals.

Abstract

Objective: Little is known about the progression of dopaminergic dysfunction in LRRK2-associated Parkinson disease (PD). We sought to characterize the neurochemical progression with multitracer PET in asymptomatic members of parkinsonian kindred (family D, Western Nebraska) carrying LRRK2 (R1441C) mutation. Method: Thirteen family D subjects underwent PET scans of presynaptic dopaminergic integrity and five subjects were rescanned 2 to 3 years later. Results: In subjects 8, 9 (mutation carriers), and 13 (genealogically at risk subject), there was a decline in PET markers over the course of the study that was significantly greater than the expected rate of decline in healthy controls. Reduced dopamine transporter binding was the earliest indication of subclinical dopaminergic dysfunction and progression to clinical disease was generally associated with the emergence of abnormal fluorodopa uptake. Conclusion: PET study of presymptomatic members of our LRRK2 kindred revealed dopaminergic dysfunction that progressed over time. This represents an ideal group to study the natural history of early disease and the potential effects of neuroprotective interventions.

Url:

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2824449

Affiliations:

Canada, États-Unis

Le document en format XML

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<term>Aged</term>
<term>Disease Progression</term>
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<term>Dopamine Plasma Membrane Transport Proteins (metabolism)</term>
<term>Dysfunction</term>
<term>Emission tomography</term>
<term>Female</term>
<term>Follow-Up Studies</term>
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<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Linear Models</term>
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<term>Middle Aged</term>
<term>Nervous system diseases</term>
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<term>Parkinson Disease (genetics)</term>
<term>Parkinson Disease (metabolism)</term>
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<term>Protein-Serine-Threonine Kinases (genetics)</term>
<term>Putamen (metabolism)</term>
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<term>Female</term>
<term>Follow-Up Studies</term>
<term>Humans</term>
<term>Leucine-Rich Repeat Serine-Threonine Protein Kinase-2</term>
<term>Linear Models</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Predictive Value of Tests</term>
<term>Radiopharmaceuticals</term>
</keywords>
<keywords scheme="Pascal" xml:lang="fr"><term>Pathologie du   système nerveux</term>
<term>Trouble fonctionnel</term>
<term>Tomoscintigraphie</term>
<term>Tomographie par émission de positons</term>
</keywords>
</textClass>
</profileDesc>
</teiHeader>
<front><div type="abstract" xml:lang="en">Objective: Little is known about the progression of dopaminergic dysfunction in LRRK2-associated Parkinson disease (PD). We sought to characterize the neurochemical progression with multitracer PET in asymptomatic members of parkinsonian kindred (family D, Western Nebraska) carrying LRRK2 (R1441C) mutation. Method: Thirteen family D subjects underwent PET scans of presynaptic dopaminergic integrity and five subjects were rescanned 2 to 3 years later. Results: In subjects 8, 9 (mutation carriers), and 13 (genealogically at risk subject), there was a decline in PET markers over the course of the study that was significantly greater than the expected rate of decline in healthy controls. Reduced dopamine transporter binding was the earliest indication of subclinical dopaminergic dysfunction and progression to clinical disease was generally associated with the emergence of abnormal fluorodopa uptake. Conclusion: PET study of presymptomatic members of our LRRK2 kindred revealed dopaminergic dysfunction that progressed over time. This represents an ideal group to study the natural history of early disease and the potential effects of neuroprotective interventions.</div>
</front>
</TEI>
<affiliations><list><country><li>Canada</li>
<li>États-Unis</li>
</country>
</list>
<tree><country name="Canada"><noRegion><name sortKey="Nandhagopal, R" sort="Nandhagopal, R" uniqKey="Nandhagopal R" first="R." last="Nandhagopal">R. Nandhagopal</name>
</noRegion>
<name sortKey="Mak, E" sort="Mak, E" uniqKey="Mak E" first="E." last="Mak">E. Mak</name>
<name sortKey="Mccormick, S" sort="Mccormick, S" uniqKey="Mccormick S" first="S." last="Mccormick">S. Mccormick</name>
<name sortKey="Mckenzie, J" sort="Mckenzie, J" uniqKey="Mckenzie J" first="J." last="Mckenzie">J. Mckenzie</name>
<name sortKey="Ruth, T J" sort="Ruth, T J" uniqKey="Ruth T" first="T. J." last="Ruth">T. J. Ruth</name>
<name sortKey="Schulzer, M" sort="Schulzer, M" uniqKey="Schulzer M" first="M." last="Schulzer">M. Schulzer</name>
<name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V." last="Sossi">V. Sossi</name>
<name sortKey="Sossi, V" sort="Sossi, V" uniqKey="Sossi V" first="V." last="Sossi">V. Sossi</name>
<name sortKey="Stoessl, A J" sort="Stoessl, A J" uniqKey="Stoessl A" first="A. J." last="Stoessl">A. J. Stoessl</name>
</country>
<country name="États-Unis"><noRegion><name sortKey="Strongosky, A" sort="Strongosky, A" uniqKey="Strongosky A" first="A." last="Strongosky">A. Strongosky</name>
</noRegion>
<name sortKey="Farrer, M J" sort="Farrer, M J" uniqKey="Farrer M" first="M. J." last="Farrer">M. J. Farrer</name>
<name sortKey="Wszolek, Z K" sort="Wszolek, Z K" uniqKey="Wszolek Z" first="Z. K." last="Wszolek">Z. K. Wszolek</name>
</country>
</tree>
</affiliations>
</record>

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La maladie de Parkinson au Canada (serveur d'exploration)

Progression of dopaminergic dysfunction in a LRRK2 kindred : A multitracer PET study

Progression of dopaminergic dysfunction in a LRRK2 kindred : A multitracer PET study

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	La maladie de Parkinson au Canada (serveur d'exploration)
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