Nadya Pyatigorskaya1,2, Michael Sharman1, Jean-Christophe Corvol1,3,4, Romain Valabregue1,3, Lydia Yahia-Cherif1,2,3, Fabrice Poupon5, Florence Cormier-Dequaire1,3,4, Hartwig Siebner6, Stephan Klebe1,3,4,7,8, Marie Vidailhet3,9, Alexis Brice1,3,7, Stephane Lehéricy1,2,3. 1. Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France. 2. Assistance Publique Hôpitaux de Paris, Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France. 3. ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France. 4. Assistance Publique Hôpitaux de Paris, INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux, Pitié-Salpêtrière Hospital, Paris, France. 5. NeuroSpin, Commissariat à l'Energie Atomique (CEA), Gif-Sur-Yvette, France. 6. Hvidovre Hospital, University of Copenhagen, Centre for Functional and Diagnostic Imaging and Research, Danish Research Centre for Magnetic Resonance (DRCMR). 7. Assistance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique, Hôpital Pitié-Salpêtrière, Paris, France. 8. University Hospital of Würzburg, Würzburg, Germany. 9. Assistance Publique Hôpitaux de Paris, Clinique des mouvements anormaux, Département des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
Abstract
OBJECTIVES: The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate. METHODS: Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus. RESULTS: The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values. CONCLUSION: These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.
OBJECTIVES: The goal of this work was to investigate iron deposition in the basal ganglia and thalamus in symptomatic and asymptomatic leucine-rich repeat kinase 2 (LRRK2) and Parkin-associated Parkinson's disease (PD), using R2* relaxometry rate. METHODS: Twenty subjects with genetic PD (four symptomatic and two asymptomatic Parkin subjects, nine symptomatic and five asymptomatic LRRK2 subjects) were compared with 20 patients with idiopathic PD (IPD) and 20 healthy subjects. Images were obtained at 3 teslas, using multi-echo T2 and T2* sequences. R2 and R2* values were calculated in the substantia nigra (SN), the striatum, the globus pallidus, and the thalamus. RESULTS: The R2* values in the SN were increased in IPD and mutation-carrying patients as compared with controls and in mutation-carrying patients as compared with IPD. Asymptomatic mutation carriers showed higher R2* values than controls and did not differ from IPD patients. No changes were seen in the other structures or in R2 values. CONCLUSION: These results are consistent with increased iron load in LRRK2- and Parkin-mutation carriers. The increased R2* in asymptomatic PD-mutation carriers suggests that iron deposition occurs early during the preclinical phase of the disease. R2* measurements may be used as markers for investigating nigrostriatal damage in preclinical mutation-carrying patients.
Authors: Adamantios Mamais; Jillian H Kluss; Luis Bonet-Ponce; Natalie Landeck; Rebekah G Langston; Nathan Smith; Alexandra Beilina; Alice Kaganovich; Manik C Ghosh; Laura Pellegrini; Ravindran Kumaran; Ioannis Papazoglou; George R Heaton; Rina Bandopadhyay; Nunziata Maio; Changyoun Kim; Matthew J LaVoie; David C Gershlick; Mark R Cookson Journal: PLoS Biol Date: 2021-12-16 Impact factor: 8.029
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