DJ-1 and αSYN in LRRK2 CSF do not correlate with striatal dopaminergic function.
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.
Department of Pathology, University of Washington School of Medicine, Seattle, WA 98104, USA.
Min
M
Shi
Amy R
AR
Furay
Vesna
V
Sossi
Jan O
JO
Aasly
Jeff
J
Armaly
Yu
Y
Wang
Zbigniew K
ZK
Wszolek
Ryan J
RJ
Uitti
Kazuko
K
Hasegawa
Teruo
T
Yokoyama
Cyrus P
CP
Zabetian
James B
JB
Leverenz
A Jon
AJ
Stoessl
Jing
J
Zhang
D015415:Biomarkers / Q000134:cerebrospinal fluid; D002247:Carbon Isotopes; D003342:Corpus Striatum / Q000000981:diagnostic imaging / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000134:cerebrospinal fluid*; D007564:Japan; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D008182:Luria-Nebraska Neuropsychological Battery; D008297:Male; D008774:Methylphenidate; D009664:Norway; D015513:Oncogene Proteins / Q000134:cerebrospinal fluid*; D010300:Parkinson Disease / Q000134:cerebrospinal fluid* / Q000175:diagnosis*; D049268:Positron-Emission Tomography; D000071617:Protein Deglycase DJ-1; D017346:Protein Serine-Threonine Kinases / Q000134:cerebrospinal fluid*; D013223:Statistics as Topic; D013747:Tetrabenazine / Q000031:analogs & derivatives; D014481:United States; D051844:alpha-Synuclein / Q000134:cerebrospinal fluid*
D015415:Biomarkers; D002247:Carbon Isotopes; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D051844:alpha-Synuclein; D019788:Fluorodeoxyglucose F18; D008774:Methylphenidate; C032811:dihydrotetrabenazine; C495280:LRRK2 protein, human; D000071158:Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; D017346:Protein Serine-Threonine Kinases; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1; D004298:Dopamine; D013747:Tetrabenazine