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Extrastriatal SPECT-DAT uptake correlates with clinical and biological features of de novo Parkinson's disease.

Frederic Sampedro | Juan Marín-Lahoz | Saul Martínez-Horta | Valle Camacho | Diego-Alfonso Lopez-Mora | Javier Pagonabarraga | Jaime Kulisevsky
Neurobiology of aging | 2021

Striatal dopamine transporter (DAT) uptake assessment through I123-Ioflupane Single-Pphoton Emission Computed Tomography (SPECT) provides valuable information about the dopaminergic denervation occurring in Parkinson's disease (PD). However, little is known about the clinical or biological relevance of extrastriatal DAT uptake in PD. Here, from the Parkinson's Progression Markers Initiative, we studied 623 participants (431 PD and 192 healthy controls) with available SPECT data. Even though striatal denervation was undoubtedly the imaging hallmark of PD, extrastriatal DAT uptake was also reduced in patients with PD. Topographically, widespread frontal but also temporal and posterior cortical regions showed lower DAT uptake in PD patients with respect to healthy controls. Importantly, a longitudinal voxelwise analysis confirmed an active one-year loss of extrastriatal DAT uptake within the PD group. Extrastriatal DAT uptake also correlated with the severity of motor symptoms, cognitive performance, and cerebrospinal fluid α-synuclein levels. In addition, we found an association between the Catechol-O-methyltransferase val158met genotype and extrastriatal DAT uptake. These results highlight the clinical and biological relevance of extrastriatal SPECT-DAT uptake in PD.

Pubmed ID: 33212336

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Covance (tool)

RRID:SCR_001224

A contract research organization providing drug development and animal testing services. Under the name Covance Research Products Inc., based in Denver, Pennsylvania, the company also deals in the import, breeding and sale of laboratory animals. It breeds dogs, rabbits, guinea pigs, non-human primates, and pigs, and runs the largest non-human primate laboratory in Germany. (Wikipedia)

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MRIcron (tool)

RRID:SCR_002403

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Parkinson's Progression Markers Initiative (tool)

RRID:SCR_006431

An observational longitudinal clinical study partnership to identify and validate biomarkers of Parkinson disease (PD) progression and provide easy and open web-based access to the comprehensive set of correlated clinical data and biospecimens, information, and biosamples acquired from PD and age and gender matched healthy control subjects to the research community. The data and specimens have been collected in a standardized manner under strict protocols and includes clinical (demographic, motor and non-motor, cognitive and neurobehavioral), imaging (raw and processed MRI, SPECT and DAT), and blood chemistry and hematology subject assessments and biospecimen inventories (serum, plasma, whole blood, CSF, DNA, RNA and urine). All data are de-identified to protect patient privacy. PPMI will be carried out over five years at 21 clinical sites in the United States and Europe and requires the participation of 400 Parkinson's patients and 200 control participants. The PPMI database provides researchers with access to correlated clinical and imaging data, along with annotated biospecimens, all available within an open access system that encourages data sharing (http://www.ppmi-info.org/access-data-specimens/). The website hosts an Ongoing Analysis section to keep the scientific community apprised of analyses being completed, in hopes of stimulating collaborations between researchers who are using PPMI data and specimens.

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