Journal
TRANSLATIONAL NEURODEGENERATION
Volume 9, Issue 1, Pages -Publisher
BMC
DOI: 10.1186/s40035-020-00192-4
Keywords
Parkinson's disease; LRRK2 mutation carriers; Alpha-synuclein oligomers; Biomarkers; Inflammatory markers
Categories
Funding
- Qatar National Research Fund (NPRP) [8-517-3-112]
- Qatar Biomedical Research Institute [SF 2007-007]
Ask authors/readers for more resources
Background Asymptomatic carriers of leucine-rich repeat kinase 2 (LRRK2) gene mutations constitute an ideal population for discovering prodromal biomarkers of Parkinson's disease (PD). In this study, we aim to identify CSF candidate risk biomarkers of PD in individuals with LRRK2 mutation carriers. Methods We measured the levels of CSF total- (t-), oligomeric (o-) and phosphorylated S129 (pS129-) alpha-syn, total-tau (tTau), phosphorylated threonine 181 tau (pTau), amyloid-beta 40 (A beta-40), amyloid-beta-42 (A beta-42) and 40 inflammatory chemokines in symptomatic (n = 23) and asymptomatic (n = 51) LRRK2 mutation carriers, subjects with a clinical diagnosis of PD (n = 60) and age-matched healthy controls (n = 34). General linear models corrected for age and gender were performed to assess differences in CSF biomarkers between the groups. Markers that varied significantly between the groups were then analyzed using backward-elimination logistic regression analysis to identify an ideal biomarkers panel of prodromal PD. Results Discriminant function analysis revealed low levels of CSF t-alpha-syn, high levels of CSF o-alpha-syn and TNF-alpha best discriminated asymptomatic LRRK2 mutation carriers from both symptomatic PD and healthy controls. Assessing the discriminative power using receiver operating curve analysis, an area under the curve > 0.80 was generated. Conclusions The current study suggests that CSF t-, o-alpha-syn and TNF-alpha are candidate risk biomarkers for the detection of PD at the prodromal stage. Our findings also highlight the dynamic interrelationships between CSF proteins and the importance of using a biomarkers' panel approach for an accurate and timely diagnosis of PD.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available