title: High nigral iron deposition in LRRK2 and Parkin mutation carriers using R2* relaxometry.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|Assistance Publique Hôpitaux de Paris, Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Nadya
authors.initials: N
authors.lastname: Pyatigorskaya
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Sharman
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.|Assistance Publique Hôpitaux de Paris, INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Corvol
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Valabregue
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|Assistance Publique Hôpitaux de Paris, Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.
authors.forename: Lydia
authors.initials: L
authors.lastname: Yahia-Cherif
authors.affiliation: NeuroSpin, Commissariat à l'Energie Atomique (CEA), Gif-Sur-Yvette, France.
authors.forename: Fabrice
authors.initials: F
authors.lastname: Poupon
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.|Assistance Publique Hôpitaux de Paris, INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux, Pitié-Salpêtrière Hospital, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Cormier-Dequaire
authors.affiliation: Hvidovre Hospital, University of Copenhagen, Centre for Functional and Diagnostic Imaging and Research, Danish Research Centre for Magnetic Resonance (DRCMR).
authors.forename: Hartwig
authors.initials: H
authors.lastname: Siebner
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.|Assistance Publique Hôpitaux de Paris, INSERM, Centre d'Investigation Clinique (CIC9503), Département des Maladies du Système Nerveux, Pitié-Salpêtrière Hospital, Paris, France.|Assistance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique, Hôpital Pitié-Salpêtrière, Paris, France.|University Hospital of Würzburg, Würzburg, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Klebe
authors.affiliation: ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.|Assistance Publique Hôpitaux de Paris, Clinique des mouvements anormaux, Département des Maladies du Système Nerveux, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.
authors.forename: Marie
authors.initials: M
authors.lastname: Vidailhet
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.|Assistance Publique Hôpitaux de Paris, Département de Génétique et Cytogénétique, Hôpital Pitié-Salpêtrière, Paris, France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Brice
authors.affiliation: Institut du Cerveau et de la Moelle épinière-ICM, Centre de NeuroImagerie de Recherche-CENIR, Paris, France.|Assistance Publique Hôpitaux de Paris, Service de neuroradiologie, Groupe Hospitalier Pitié-Salpêtrière, Paris, France.|ICM, Université Pierre et Marie Curie (UPMC Univ Paris 6), Inserm UMR-S1127; CNRS, UMR 7225, Paris, France.
authors.forename: Stephane
authors.initials: S
authors.lastname: Lehéricy
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005917:Globus Pallidus / Q000378:metabolism; D006579:Heterozygote; D006801:Humans; D007501:Iron / Q000378:metabolism*; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D017072:Neostriatum / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D013378:Substantia Nigra / Q000378:metabolism*; D013788:Thalamus / Q000378:metabolism; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: D007501:Iron; D044767:Ubiquitin-Protein Ligases; C111567:parkin protein; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases
keywords: LRRK2; MRI; Parkin; Parkinson's disease; relaxometry