☆ 4.6 Article

DAT imaging and clinical biomarkers in relatives at genetic risk for LRRK2R1441G Parkinson's disease

MOVEMENT DISORDERS (2016)

Journal

MOVEMENT DISORDERS

Volume 31, Issue 3, Pages 335-343

Publisher

WILEY

DOI: 10.1002/mds.26478

Keywords

Parkinson's disease; DATSCAN; biomarkers; LRRK2; R1441G

Funding

Fondo de Investigacion Sanitaria-ISCIII, Spain [FIS PS09/00818]
Basque Government, Spain [GV 2009111020]

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Abstract

BackgroundThe objective of this study was to study motor and nonmotor symptoms and striatal dopaminergic denervation, as well as the relationship between them, in a cohort of asymptomatic relatives of patients with Parkinson's disease (PD) with the R1441G-leucine-rich repeat kinase 2 mutation. MethodsAsymptomatic relatives of patients with PD and this mutation were tested for the presence of the mutation and evaluated for striatal, putamenal, and caudate dopaminergic transporters using I-123-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane single-photon emission computed tomography binding ratios. Clinical and neuropsychological evaluations including timed motor tests, a smell identification test, and global cognition, attention, executive, visuospatial, and memory functions as well as depression, constipation, and rapid eye movement sleep behavior disorder were also assessed. ResultsTwenty-seven carriers and 19 noncarriers were studied. Compared with noncarriers, mutation carriers had significantly lower I-123-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl)-nortropan mean striatal (P=0.03), mean putamenal (P=0.01), and lowest putamenal (P=0.01) binding ratios. Multiple linear regression analysis showed that the carrier status and the execution of timed tests significantly predicted striatal I-123-2-carbomethoxy-3-(4-iodophenyl)-N-(3-fluoropropyl)-nortropane binding. The proportion of variation accounted for by the regression model of these variables was 69% for the putamen and 53% for the caudate nucleus. ConclusionsAsymptomatic carriers of the R1441G-leucine-rich repeat kinase 2 mutation have evidence of dopaminergic nigrostriatal denervation, mainly in the putamen, which is associated with a decline in the execution of complex motor tests. These tests could be early indicators of the ongoing dopaminergic deficit in this group at risk of PD. (c) 2015 International Parkinson and Movement Disorder Society

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A More Homogeneous Phenotype in Parkinson's Disease Related to R1441G Mutation in the LRRK2 Gene

Ana Vinagre-Aragon, David Campo-Caballero, Elisabet Mondragon-Rezola, Lara Pardina-Vilella, Haizea Hernandez Eguiazu, Ana Gorostidi, Ioana Croitoru, Alberto Bergareche, Javier Ruiz-Martinez

Summary: Parkinson's disease exhibits clinical heterogeneity, primarily driven by interactions between genetic, epigenetic, and environmental factors; mutations in the LRRK2 gene are the most common genetic cause, associated with both familial and sporadic PD risk; the clinical variability of PD may be linked to LRRK2 gene mutations.

FRONTIERS IN NEUROLOGY (2021)