Dopamine turnover increases in asymptomatic LRRK2 mutations carriers

Vesna Sossi, Raul De La Fuente-Fernández, Ramachandiran Nandhagopal, Michael Schulzer, Jessamyn McKenzie, Thomas J. Ruth, Jan O. Aasly, Matthew J. Farrer, Zbigniew K. Wszolek, Jon A. Stoessl

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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: 18F-fluorodopa to determine the effective DA distribution volume (EDV), the inverse of DA turnover, and the DA uptake rate Kocc, a marker of DA synthesis and storage; 11C-methylphenidate (MP, a DAT marker) and 11C-dihydrotetrabenazine (DTBZ, a VMAT2 marker) to estimate the binding potentials BPND_MP and BPND_DTBZ. On average, EDV showed the largest reduction from age-matched control values (42%) followed by BPND_MP (23%) and BPND_DTBZ (17%), whereas Kocc 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.

Original languageEnglish
Pages (from-to)2717-2723
Number of pages7
JournalMovement Disorders
Volume25
Issue number16
DOIs
Publication statusPublished - Dec 15 2010

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Dopamine
Mutation
Dopamine Plasma Membrane Transport Proteins
Secondary Parkinson Disease
Parkinson Disease
Asymptomatic Diseases
Methylphenidate
Positron-Emission Tomography
Reference Values

Keywords

  • Dopamine turnover
  • LRRK2 mutation
  • Parkinson's disease
  • PET imaging

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Sossi, V., De La Fuente-Fernández, R., Nandhagopal, R., Schulzer, M., McKenzie, J., Ruth, T. J., ... Stoessl, J. A. (2010). Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. Movement Disorders, 25(16), 2717-2723. https://doi.org/10.1002/mds.23356

Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. / Sossi, Vesna; De La Fuente-Fernández, Raul; Nandhagopal, Ramachandiran; Schulzer, Michael; McKenzie, Jessamyn; Ruth, Thomas J.; Aasly, Jan O.; Farrer, Matthew J.; Wszolek, Zbigniew K.; Stoessl, Jon A.

In: Movement Disorders, Vol. 25, No. 16, 15.12.2010, p. 2717-2723.

Research output: Contribution to journalArticle

Sossi, V, De La Fuente-Fernández, R, Nandhagopal, R, Schulzer, M, McKenzie, J, Ruth, TJ, Aasly, JO, Farrer, MJ, Wszolek, ZK & Stoessl, JA 2010, 'Dopamine turnover increases in asymptomatic LRRK2 mutations carriers', Movement Disorders, vol. 25, no. 16, pp. 2717-2723. https://doi.org/10.1002/mds.23356
Sossi V, De La Fuente-Fernández R, Nandhagopal R, Schulzer M, McKenzie J, Ruth TJ et al. Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. Movement Disorders. 2010 Dec 15;25(16):2717-2723. https://doi.org/10.1002/mds.23356
Sossi, Vesna ; De La Fuente-Fernández, Raul ; Nandhagopal, Ramachandiran ; Schulzer, Michael ; McKenzie, Jessamyn ; Ruth, Thomas J. ; Aasly, Jan O. ; Farrer, Matthew J. ; Wszolek, Zbigniew K. ; Stoessl, Jon A. / Dopamine turnover increases in asymptomatic LRRK2 mutations carriers. In: Movement Disorders. 2010 ; Vol. 25, No. 16. pp. 2717-2723.
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