Relationship between Substantia Nigra Neuromelanin Imaging and Dual Alpha-Synuclein Labeling of Labial Minor in Salivary Glands in Isolated Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease

Graziella Mangone; Marion Houot; Rahul Gaurav; Susana Boluda; Nadya Pyatigorskaya; Alizé Chalancon; Danielle Seilhean; Annick Prigent; Stéphane Lehéricy; Isabelle Arnulf; Jean-Christophe Corvol; Marie Vidailhet; Charles Duyckaerts; Bertrand Degos

doi:10.3390/genes13101715

Relationship between Substantia Nigra Neuromelanin Imaging and Dual Alpha-Synuclein Labeling of Labial Minor in Salivary Glands in Isolated Rapid Eye Movement Sleep Behavior Disorder and Parkinson's Disease

Genes (Basel). 2022 Sep 24;13(10):1715. doi: 10.3390/genes13101715.

Authors

Graziella Mangone^{1

2}, Marion Houot^{1

3

4}, Rahul Gaurav^{1

5

6}, Susana Boluda^{1

7}, Nadya Pyatigorskaya^{1

5

6}, Alizé Chalancon^{1

2}, Danielle Seilhean^{1

7}, Annick Prigent⁸, Stéphane Lehéricy^{1

5

6}, Isabelle Arnulf^{1

9}, Jean-Christophe Corvol^{1

2}, Marie Vidailhet^{1

2

6}, Charles Duyckaerts^{1

7}, Bertrand Degos^{10

11}

Affiliations

¹ Centre National de la Recherche Scientifique CNRS, Institut National de la Santé Et de la Recherche Médicale INSERM, Institut du Cerveau ICM, Sorbonne Université, 47-83 Bd de l'Hôpital, 75013 Paris, France.
² Clinical Investigation Center for Neurosciences, Department of Neurology, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.
³ Centre of Excellence of Neurodegenerative Disease (CoEN), AP-HP, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁴ Department of Neurology, Institute of Memory and Alzheimer's Disease (IM2A), AP-HP, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁵ Centre de NeuroImagerie de Recherche CENIR, Institut du Cerveau ICM, 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁶ Institut du Cerveau-ICM, Team "Movement Investigations and Therapeutics" (MOV'IT), 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁷ Department of Neuropathology, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁸ HYSTOMICS Platform, Centre National de la Recherche Scientifique-CNRS, Institut National de la Santé Et de la Recherche Médicale-INSERM, Institut du Cerveau-ICM, Sorbonne Université, 47-83 Bd de l'Hôpital, 75013 Paris, France.
⁹ Sleep Disorders Unit, Assistance Publique Hôpitaux de Paris, Pitié-Salpêtrière Hospital, 47-83 Bd de l'Hôpital, 75013 Paris, France.
¹⁰ Neurology Unit, Avicenne University Hospital, Hôpitaux Universitaires de Paris-Seine Saint Denis, Sorbonne Paris Nord, AP-HP, NS-PARK/FCRIN Network, 125 Route de Stalingrad, 93009 Bobigny, France.
¹¹ Dynamics and Pathophysiology of Neuronal Networks Team, Center for Interdisciplinary Research in Biology, Collège de France, PSL University, 11 Place Marcelin Berthelot, 75005 Paris, France.

Abstract

We investigated the presence of misfolded alpha-Synuclein (α-Syn) in minor salivary gland biopsies in relation to substantia nigra pars compacta (SNc) damage measured using magnetic resonance imaging in patients with isolated rapid eye movement sleep behavior disorder (iRBD) and Parkinson's disease (PD) as compared to healthy controls. Sixty-one participants (27 PD, 16 iRBD, and 18 controls) underwent a minor salivary gland biopsy and were scanned using a 3 Tesla MRI. Deposits of α-Syn were found in 15 (55.6%) PD, 7 (43.8%) iRBD, and 7 (38.9%) controls using the anti-aggregated α-Syn clone 5G4 antibody and in 4 (14.8%) PD, 3 (18.8%) iRBD and no control using the purified mouse anti-α-Syn clone 42 antibody. The SNc damages obtained using neuromelanin-sensitive imaging did not differ between the participants with versus without α-Syn deposits (irrespective of the antibodies and the disease group). Our study indicated that the α-Syn detection in minor salivary gland biopsies lacks sensitivity and specificity and does not correlate with the SNc damage, suggesting that it cannot be used as a predictive or effective biomarker for PD.

Keywords: Parkinson’s disease; alpha-Synuclein; immunostaining; microscopy; minor salivary gland biopsy; neuromelanin.

MeSH terms

Animals
Biomarkers
Mice
Parkinson Disease* / diagnostic imaging
Parkinson Disease* / pathology
REM Sleep Behavior Disorder* / diagnostic imaging
REM Sleep Behavior Disorder* / pathology
Salivary Glands / metabolism
Substantia Nigra / diagnostic imaging
Substantia Nigra / metabolism
Substantia Nigra / pathology
alpha-Synuclein / metabolism

Substances

alpha-Synuclein
neuromelanin
Biomarkers

Grants and funding

The research leading to these results received funding from a grant from the France Parkinson Association, from the French State “Investissements d’Avenir” (ANR-10-IAIHU-06), and from the EDF foundation.