Early Biomarkers of Neurodegeneration in Parkinsonian Syndromes

Parkinson's disease (PD) is the most common degenerative Parkinson's syndrome and is linked, among other things, to the excessive accumulation of an abnormally aggregating protein, alpha-synuclein. Progressive Supranuclear Palsy (PSP) is another Parkinson's syndrome, linked, among other things, to the abnormal accumulation of the protein Tau, and expressed clinically by falls, early cognitive impairment and oculomotor disorders, not present in PD. The onset of these disorders is so gradual that differential diagnosis between the two diseases is only possible at a late stage, on average 3 to 5 years after the onset of symptoms.

To date, there is a lack of validated imaging biomarkers for diagnosing and monitoring PD and PSP. There is therefore an urgent need for the development of robust biomarkers capable of detecting neurodegeneration at an early stage, in order to aid differential diagnosis as soon as symptoms appear, and to potentially enable these patients to be included in specific therapeutic trials (as these diseases are pathophysiologically different) with potential neuroprotective effects.

The development of cutting-edge technologies such as 7T MRI, combined with optimized image processing methods, now enable non-invasive in vivo exploration and analysis of these small structures in terms of ion homeostasis (sodium), microstructure (volumetry, amount of iron and neuromelanin) and connectivity.


Eligibility Criteria:
For Parkinson Disease:

Inclusion Criteria:

1. Patients aged between 40 and 80
2. Fulfilling the diagnostic criteria for MPI (Postuma et al., 2015)
3. First motor symptom (rigidity, akinesia, tremor) less than 36 months ago
4. Patient entitled to or affiliated with a social security scheme
5. Patients who understood, completed and signed the consent form for study participation.

Exclusion Criteria:

1. Patient with a neurological disease of the central nervous system other than those studied (including history of stroke, repeated head trauma, documented encephalitis). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing full MRI.
4. Montreal Cognitive Assessment (MOCA) test \< 25/30
5. Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty).

For Progressive Supra-nuclear Palsy:

Inclusion criteria:

1. Patients aged 40 to 80
2. Fulfilling the diagnostic criteria for soPSP (Höglinger et al., 2017) :
3. First motor symptom (rigidity, akinesia, tremor) or falls or cognitive impairment (frontal syndrome or language disorder or cortico-basal syndrome) occurring less than 36 months ago
4. Patients benefiting from or affiliated to a social security scheme
5. Patients who have understood, completed and signed the study participation consent form

Exclusion criteria:

1. Patient with a neurological disease of the central nervous system other than those studied (including history of stroke, repeated head trauma, documented encephalitis). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing MRI.
4. Pregnant or breast-feeding woman or protected person (under guardianship, curatorship, deprived of liberty).

For Control group:

Inclusion criteria:

1. Subjects aged between 40 and 80
2. Subjects benefiting from or affiliated with a social security plan
3. Subjects who have understood, completed and signed the study participation consent form

Exclusion criteria:

1. Subjects with a known history of neurological disease of the central nervous system (e.g. Parkinson's disease, Alzheimer's, stroke, brain tumor, multiple sclerosis, amyotrophic lateral sclerosis, repeated head trauma, documented encephalitis, etc.). In case of doubt, this criterion will be left to the discretion of the principal investigator, who is a neurologist.
2. Contraindications to 7T MRI: presence of an ocular metallic foreign body (accidental shrapnel or other), pacemaker (cardiac simulator) or neurostimulator (pain treatment), cochlear implants or any implanted electronic medical equipment in general, metallic heart valve, vascular clips implanted on a cranial aneurysm.
3. Claustrophobia or any other condition preventing MRI.
4. Pregnant or breast-feeding women or protected persons (under guardianship, curatorship, deprived of liberty).