DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function

Min Shi, Amy R. Furay, Vesna Sossi, Jan O. Aasly, Jeff Armaly, Yu Wang, Zbigniew K Wszolek, Ryan J. Uitti, Kazuko Hasegawa, Teruo Yokoyama, Cyrus P. Zabetian, James B. Leverenz, A. Jon Stoessl, Jing Zhang

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Previous studies demonstrated decreased levels of DJ-1 and α-synuclein (αSYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and αSYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD. The data revealed no statistically significant relationship between PET scan evidence of loss of striatal dopaminergic function and the CSF biomarkers DJ-1 and αSYN, except for a weak correlation between DJ-1 and methylphenidate binding, suggesting that the use of these potential biomarkers on their own to screen LRRK2 gene mutation carriers for PD is not appropriate.

Original languageEnglish (US)
JournalNeurobiology of Aging
Volume33
Issue number4
DOIs
StatePublished - Apr 2012

Fingerprint

Synucleins
Corpus Striatum
Leucine
Parkinson Disease
Cerebrospinal Fluid
Phosphotransferases
Positron-Emission Tomography
Mutation
Biomarkers
Methylphenidate
Basal Ganglia
Genes
Phenotype

Keywords

  • α-synuclein
  • Biomarker
  • DJ-1
  • Gene mutation
  • LRRK2
  • Parkinson's disease

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Aging
  • Developmental Biology
  • Geriatrics and Gerontology

Cite this

Shi, M., Furay, A. R., Sossi, V., Aasly, J. O., Armaly, J., Wang, Y., ... Zhang, J. (2012). DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. Neurobiology of Aging, 33(4). https://doi.org/10.1016/j.neurobiolaging.2011.09.015

DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. / Shi, Min; Furay, Amy R.; Sossi, Vesna; Aasly, Jan O.; Armaly, Jeff; Wang, Yu; Wszolek, Zbigniew K; Uitti, Ryan J.; Hasegawa, Kazuko; Yokoyama, Teruo; Zabetian, Cyrus P.; Leverenz, James B.; Stoessl, A. Jon; Zhang, Jing.

In: Neurobiology of Aging, Vol. 33, No. 4, 04.2012.

Research output: Contribution to journalArticle

Shi, M, Furay, AR, Sossi, V, Aasly, JO, Armaly, J, Wang, Y, Wszolek, ZK, Uitti, RJ, Hasegawa, K, Yokoyama, T, Zabetian, CP, Leverenz, JB, Stoessl, AJ & Zhang, J 2012, 'DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function', Neurobiology of Aging, vol. 33, no. 4. https://doi.org/10.1016/j.neurobiolaging.2011.09.015
Shi, Min ; Furay, Amy R. ; Sossi, Vesna ; Aasly, Jan O. ; Armaly, Jeff ; Wang, Yu ; Wszolek, Zbigniew K ; Uitti, Ryan J. ; Hasegawa, Kazuko ; Yokoyama, Teruo ; Zabetian, Cyrus P. ; Leverenz, James B. ; Stoessl, A. Jon ; Zhang, Jing. / DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function. In: Neurobiology of Aging. 2012 ; Vol. 33, No. 4.
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abstract = "Previous studies demonstrated decreased levels of DJ-1 and α-synuclein (αSYN) in human cerebrospinal fluid (CSF) in patients with Parkinson's disease (PD), but neither marker correlated with PD severity, raising the possibility that they may be excellent progression markers during early or preclinical phases of PD. Individuals carrying the leucine-rich repeat kinase 2 (LRRK2) gene mutation are at increased risk for PD, and the phenotype of LRRK2 patients is almost identical to sporadic PD. To determine whether dopaminergic dysfunction in the basal ganglia, as determined by positron emission tomography (PET) scans, correlates with CSF levels of DJ-1 and αSYN during preclinical stages, Luminex assays were used to analyze CSF samples from asymptomatic LRRK2 mutation carriers, along with carriers who presented with a clinical diagnosis of PD. The data revealed no statistically significant relationship between PET scan evidence of loss of striatal dopaminergic function and the CSF biomarkers DJ-1 and αSYN, except for a weak correlation between DJ-1 and methylphenidate binding, suggesting that the use of these potential biomarkers on their own to screen LRRK2 gene mutation carriers for PD is not appropriate.",
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