Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 4, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.09.015
Keywords
Parkinson's disease; LRRK2; Gene mutation; Biomarker; DJ-1; alpha-synuclein
Categories
Funding
- NIA NIH HHS [R01 AG033398, R01 AG033398-05, R01 AG025327] Funding Source: Medline
- NIEHS NIH HHS [R01 ES016873-03, R01 ES019277-02, R01 ES016873, R01 ES019277, R01 ES019277-01A1] Funding Source: Medline
- NINDS NIH HHS [P50 NS062684, R01 NS057567, R01 NS065070, R21 NS060252, R01 NS057567-05, P50 NS072187] Funding Source: Medline
- BLRD VA [I01 BX000531] Funding Source: Medline
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Previous studies demonstrated decreased levels of DJ-1 and alpha-synuclein (alpha SYN) 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 alpha SYN 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 alpha SYN, 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. (C) 2012 Elsevier Inc. All rights reserved.
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