1 research outputs found
Targeted Discovery and Validation of Plasma Biomarkers of Parkinson’s Disease
Despite
extensive research, an unmet need remains for protein biomarkers
of Parkinson’s disease (PD) in peripheral body fluids, especially
blood, which is easily accessible clinically. The discovery of such
biomarkers is challenging, however, due to the enormous complexity
and huge dynamic range of human blood proteins, which are derived
from nearly all organ systems, with those originating specifically
from the central nervous system (CNS) being exceptionally low in abundance.
In this investigation of a relatively large cohort (∼300 subjects),
selected reaction monitoring (SRM) assays (a targeted approach) were
used to probe plasma peptides derived from glycoproteins previously
found to be altered in the CNS based on PD diagnosis or severity.
Next, the detected peptides were interrogated for their diagnostic
sensitivity and specificity as well as the correlation with PD severity,
as determined by the Unified Parkinson’s Disease Rating Scale
(UPDRS). The results revealed that 12 of the 50 candidate glycopeptides
were reliably and consistently identified in plasma samples, with
three of them displaying significant differences among diagnostic
groups. A combination of four peptides (derived from PRNP, HSPG2,
MEGF8, and NCAM1) provided an overall area under curve (AUC) of 0.753
(sensitivity: 90.4%; specificity: 50.0%). Additionally, combining
two peptides (derived from MEGF8 and ICAM1) yielded significant correlation
with PD severity, that is, UPDRS (<i>r</i> = 0.293, <i>p</i> = 0.004). The significance of these results is at least
two-fold: (1) it is possible to use a targeted approach to identify
otherwise very difficult to detect CNS related biomarkers in peripheral
blood and (2) the novel biomarkers, if validated in independent cohorts,
can be employed to assist with clinical diagnosis of PD as well as
monitoring disease progression