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Dopamine turnover increases in asymptomatic LRRK2 mutations carriers
Author(s) -
Sossi Vesna,
de la FuenteFernández Raul,
Nandhagopal Ramachandiran,
Schulzer Michael,
McKenzie Jessamyn,
Ruth Thomas J.,
Aasly Jan O.,
Farrer Matthew J.,
Wszolek Zbigniew K.,
Stoessl Jon A.
Publication year - 2010
Publication title -
movement disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.352
H-Index - 198
eISSN - 1531-8257
pISSN - 0885-3185
DOI - 10.1002/mds.23356
Subject(s) - asymptomatic , dopaminergic , medicine , endocrinology , dopamine transporter , dopamine , parkinson's disease , lrrk2 , chemistry , disease
Abstract Increase in dopamine (DA) turnover was found to occur early in symptomatic Parkinson's disease (PD) and to be functionally related to the dopamine transporter (DAT). The objectives of this study were to examine changes in DA turnover in the asymptomatic PD phase; to compare them with changes in other dopaminergic markers, and to investigate a possible relationship between DAT and DA turnover. Eight subjects from families at increased risk of PD due to LRRK2 mutation were investigated. Positron emission tomography imaging was performed with: 18 F‐fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate K occ , a marker of DA synthesis and storage; 11 C‐methylphenidate (MP, a DAT marker) and 11 C‐dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BP ND_MP and BP ND_DTBZ . On average, EDV showed the largest reduction from age‐matched control values (42%) followed by BP ND _ MP (23%) and BP ND _ DTBZ (17%), whereas K occ remained in the normal range for all subjects. No correlation was found between EDV and any other marker. DA turnover was found to be elevated in asymptomatic mutation carriers at increased risk of PD. Such change was determined to be larger than and statistically independent from changes observed with the other markers. These results support a compensatory role of increased DA turnover in presymptomatic disease and indicate that at this stage, in contrast to the symptomatic PD phase, increased turnover is not related to DAT. © 2010 Movement Disorder Society