Perspective: Identification of genetic variants associated with dopaminergic compensatory mechanisms in early Parkinson's disease

Lior Greenbaum*, Mordechai Lorberboym, Eldad Melamed, Amihai Rigbi, Yael Barhum, Yoav Kohn, Alexander Khlebtovsky, Bernard Lerer, Ruth Djaldetti

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Parkinson's disease (PD) is slowly progressive, and heterogeneity of its severity among individuals may be due to endogenous mechanisms that counterbalance the striatal dopamine loss. In this perspective paper, we introduce a neuroimaging-genetic approach to identify genetic variants, which may contribute to this compensation. First, we briefly review current known potential compensatory mechanisms for premotor and early disease PD, located in the striatum and other brain regions. Then, we claim that a mismatch between69 mild symptomatic disease, manifested by low motor score on the Unified PD Rating Scale (UPDRS), and extensive Nigro-Striatal (NS) degeneration, manifested by reduced uptake of [123I]FP-CIT, is indicative of compensatory processes. If genetic variants are associated with the severity of motor symptoms, while the level of striatal terminals degeneration measured by ligand uptake is taken into account and controlled in the analysis, then these variants may be involved in functional compensatory mechanisms for striatal dopamine deficit. To demonstrate feasibility of this approach, we performed a small "proof of concept" study (candidate gene design) in a sample of 28 Jewish PD patients, and preliminary results are presented.

Original languageEnglish
Article numberArticle 52
JournalFrontiers in Neuroscience
Issue number7 APR
DOIs
StatePublished - 2013

Keywords

  • Compensatory mechanisms
  • FP-CIT SPECT
  • Neuroimaging genetics
  • Parkinson's disease
  • Tyrosine hydroxylase

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