Identification of a Biomarker Predictive of Evolution of Parkinson Disease (GLIAPARK)

Brain Microglial Activation in the Early Stage of the Parkinson's Disease: a Predictive Biomarker of the Evolution?

Phase II, Open-labeled, Prospective, Multi-center study of assessing the link between microglial activation and dopaminergic denervation kinetics in the early stage of Parkinson disease, by using the imaging of [18F]DPA-714 a new ligand of Translocator Protein-18 kDa (TSPO) by Positron Emission Tomography (PET).

The Parkinson's disease ( MP) is a frequent but heterogeneous neurodegenerative disease in term of clinical presentation(display) and evolutionary profile. The therapeutic coverage(care) of the patients would thus be personalized Such an approach remains still in its infancy in 2017. Better know the factors which determine the evolutionary clinical subcategories is a major question of the current researches on the Parkinson disease. Nigrostriaial inflammation is an interesting candidate. Microglia activation is closely associated with the degenerative process. Development of the molecular imaging allows to study nigrostriatal inflammation in vivo in human by positron emission tomography (PET) by using the radiotracer of the protein of translocation of 18KDa ( TSPO), considered as a marker of microglia activation Some studies showed an increase of the inflammation in the striatum and in the substantia nigra, the sites of the dopaminergic degeneration (The lesional core of the Parkinson disease is the damage of the dopaminergic nigrostriatale way). However data remain rare and concern small number of patients. Some data are inconsistent because of problems of specificity of the ligands used and variation between populations of studied patients (duration of disease evolution). In this study, investigators suggest studying by imaging TEP using a ligand new of the TSPO, [18F]DPA-714, microglial brain activation in the early stage of the Parkinson disease and determine wether it is predictive of speed of disease progression.

One PET scan using [18F]DPA-714 is done at M2 between two [123I]FP-CIT scan (DaTscan) done at M1 and M35. Neuropsychological assessment is done at M0, M18 and M36

Coefficient of correlation between level of microglial striatal activation and the And the dopaminergic denervation kinetics

Coefficient of correlation between the striatal microglial activation level measured by PET imaging [binding potential (BP) of 18F-DPA-714 in the striatum] and dopaminergic denervation kinetics obtained from two 123I-FP-CIT (DaTscan) scans

Analyze the relationship between the level of microglial activation in the black substance at the early stage of MP and the dopaminergic denervation kinetics

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic symptoms (motors)

Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Evaluate the link between the level of striatal microglial activation at inclusion and:the severity of dopaminergic symptoms (non-motors)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Detection of paradoxical sleep disorder, according to the questionnaire for the detection of REM sleep disorders

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of symptoms considered mainly non-dopaminergic (non-motor)

Evaluate the relation between the level of striatal microglial activation at inclusion and the severity of dopaminergic denervation at baseline (DaTscan initial)

Dopaminergic denervation at inclusion will be measured by the binding potential (BP) of ioflupane (123I-FP-CIT) by regions of interest in the caudate and putamen of the striatum

Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Evaluate the link between the level of microglial activation in the black substance and outcome 3 to outcome 57

Evaluate the link between the level of striatal microglial activation and the level of activation in other brain regions (black substance, bridge and cortex)

The level of cortical microglial activation measured by fixation of the radioligand 18F-DPA-714, on some volumes of interest in the brain

Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Assess the relationship between the level of microglial activation in the extra-striatal cortical (cortex and brain stem) regions and the presence of non-motor and axial motor symptoms.

Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation Evaluate the relationship between the level of nigrostriatal microglial activation

Evaluate the link between the level of nigrostriatal microglial activation and the serum level of biological markers of inflammation

Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Evaluate the relationship between the level of nigrostriatal microglial activation and the serum uric acid level at 0, 18 and 36 months

Inclusion Criteria: Patients having a Parkinson's disease diagnosed according to the criteria UKPDSBB. Diagnosis done less than three years before the date the inclusion. Patient Age at diagnosis : between 40 and 65 years. Absence of clinical arguments for an associated neurovascular pathology. Written consent obtained. HAB polymorphism in the genotyping of TSPO gene. Brain MRI without following abnormalities: cortical or sub-cortical atrophy or hippocampal atrophy (Scheltens score ≥2), vascular encephalopathy (Fazekas score > 2, > 10 microbleed) or showing signs in favour of atypical parkinson syndrome. Exclusion Criteria: Pregnant woman Minor Adult protected by the law Contraindication to PET-scan Contraindication to brain MRI History of inflammatory or dysimmune chronic disease History of psychiatric disease or drug addiction History of cognitive disorders (MMS<26) Hypersensibility to iodine derivates or one of these components Long-term Treatments which can interfere in neuroinflammation process Treatments / substances susceptible to interfere with the 18F-DPA-714 TSPO gene Polymorphisms rs6971 corresponding to groups of affinity of low affinity (LAB=Low Affinity Binder) or moderated MAB = Mixed Affinity Binder) Modification of diagnosis of Parkinson disease during follow-up, in particular towards an atypical parkinson-like syndrome