Serotonin and dopamine transporter PET changes in the premotor phase of LRRK2 parkinsonism: cross-sectional studies
The Lancet Neurology
Volume 16, No. 5, p351–359, May 2017
Dr Daryl J Wile, Pankaj A Agarwal, DM, Prof Michael Schulzer, PhD, Edwin Mak, BASc, Katherine Dinelle, MSc, Elham Shahinfard, PhD, Nasim Vafai, MASc, Kazuko Hasegawa, PhD, Prof Jing Zhang, PhD, Jessamyn McKenzie, LPN, Nicole Neilson, RN, Audrey Strongosky, BA, Prof Ryan J Uitti, MD, Mark Guttman, MD, Cyrus P Zabetian, MD, Prof Yu-Shin Ding, PhD, Mike Adam, PhD, Prof Jan Aasly, MD, Prof Zbigniew K Wszolek, MD, Prof Matthew Farrer, PhD, Prof Vesna Sossi, PhD, Prof A Jon Stoessl, MD
Abstract
Background
People with Parkinson’s disease can show premotor neurochemical changes in the dopaminergic and non-dopaminergic systems. Using PET, we assessed whether dopaminergic and serotonin transporter changes are similar in LRRK2 mutation carriers with Parkinson’s disease and individuals with sporadic Parkinson’s disease, and whether LRRK2 mutation carriers without motor symptoms show PET changes.
Methods
We did two cross-sectional PET studies at the Pacific Parkinson’s Research Centre in Vancouver, BC, Canada. We included LRRK2 mutation carriers with or without manifest Parkinson’s disease, people with sporadic Parkinson’s disease, and age-matched healthy controls, all aged 18 years or older. People with Parkinson’s disease were diagnosed by a neurologist with movement disorder training, in accordance with the UK Parkinson’s Disease Society Brain Bank criteria. LRRK2 carrier status was confirmed by bidirectional Sanger sequencing. In the first study, LRRK2 mutation carriers with or without manifest Parkinson’s disease who were referred for investigation between July, 1999, and January, 2012, were scanned with PET tracers for the membrane dopamine transporter, and dopamine synthesis and storage (18F-6-fluoro-L-dopa; 18F-FDOPA). We compared findings with those in people with sporadic Parkinson’s disease and age-matched healthy controls. In the second study, distinct groups of LRRK2 mutation carriers, individuals with sporadic Parkinson’s disease, and age-matched healthy controls seen from November, 2012, to May, 2016, were studied with tracers for the serotonin transporter and vesicular monoamine transporter 2 (VMAT2). Striatal dopamine transporter binding, VMAT2 binding, 18F-FDOPA uptake, and serotonin transporter binding in multiple brain regions were compared by ANCOVA, adjusted for age.
