Mov Disord: A number of common blood markers can be used for early Parkinson's disease surveillance

Parkinson's disease (PD) is an increasingly common, progressive, and complex neurodegenerative disease that primarily (but is not limited to) dopaminergic neurons
in the substantia nigra compact.

In the past, the search for biomarkers of PD was mainly based on hypotheses, and to date, unique, objective, clinically meaningful biomarkers have been lacking
.
First of all, the clinical manifestations of the disease are extremely heterogeneous, clinically overlapping
with many other parkinsonisms.
Second, diagnosis occurs only when most of the affected neurons have already degenerated, so the search for biomarkers for valid diagnosis and prognosis needs to be expanded
.

To identify novel biomarkers associated with disease processes, Michael Bartl, Department of Neurology, University Medical Center Göttingen, Germany, et al.
analyzed well-characterized new-onset PD (DeNoPa) patient cohorts and matched HCs Different combinations of markers in longitudinal samples, assessing established markers of neuronal function, inflammation, and cardiovascular risk in deep phenotypic PD by high-throughput sandwich immune multiplex
combinations.

The study used the proximity extension test technique to follow 109 patients with PD who were not treated at baseline (BL, 2-, 4-, and 6-year follow-up and 96 healthy control patients (HC; 273 plasma markers at 2 and 4 years follow-up
.
74 participants (37 PD patients and 37 healthy controls) using the same platform using the Parkinson's Progress Markers Initiative The baseline plasma is independently verified
.
These markers were correlated with
6 years of clinical follow-up, including motor and cognitive progress.

Baseline 35 plasma markers were differently expressed in PD, and atherosclerosis risk markers such as E-selectin and β _2-integrin were downregulated
.
Conversely, markers of the plasminogen activation system, such as urokinase-type plasminogen activator, are reduced
.

Volcano plot
of plasma differentially expressed proteins analyzed by OLINK panel of new-onset Parkinson's disease (PD) cohort.
The mark displayed from the axis to the left is adjusted upwards; In plasma samples from patients with PD, the expression of the marker shown on the right is downregulated
.

Neurospecific markers such as fibroblast growth factor 21 and peptidase inhibitor 3 suggest elevated
peripheral proteins for neurodegeneration and inflammation.

Some markers, such as interleukin-6 and cystatin B, are associated
with cognitive decline and progression of motor symptoms during follow-up.
These findings were independently validated
in the Parkinson's Progress Markers program.

Multiplex biomarker analysis of plasma samples showed a decrease
in marker levels commonly associated with CVR in the study's PD cohort.
However, significant changes in the plasminogen activator system may result in decreased α-synuclein cleavage, which in turn increases aggregation, neuroinflammation, and degeneration
.
Inflammatory markers are associated with cognitive and motor impairment in Parkinson's disease, but are not specific.

In particular, the recognized clinical marker IL-6 should be considered a biomarker of disease severity and progression
.
IL-6 and cystatin B are also potential PD-targeted drugs
.
The findings were validated in PD patient samples from a multicenter PPMI trial, further supporting previously described changes
in the regulatory mechanisms of vascular pathology and plasminogen activation in PD patients.

Original source

Bartl M, Dakna M, Schade S, et al.
Blood Markers of Inflammation, Neurodegeneration, and Cardiovascular Risk in Early Parkinson's Disease [published online ahead of print, 2022 Oct 20].
Mov Disord.
2022; 10.
1002/mds.
29257.
doi:10.
1002/mds.
29257