Parkinson’s disease (PD) is one of
the highly prevalent neurodegenerative diseases which lack a specific diagnosis
for the clinical evaluation of disease progression as well as its treatment. A
novel research study revealed that detection of αSyn aggregates circulating in
the cerebrospinal fluid (CSF) may provide an opportunity for a sensitive and
specific biochemical diagnosis of PD.
Parkinson’s disease (PD) is one of the
degenerative disorders caused by aggregation and deposition of α-synuclein
(αSyn) in the brain and leads to abnormalities in the motor activities and gait
pattern.
Usually, α-synuclein follows a
seeding-nucleation mechanism that depends on the slow formation of
seeding-competent oligomers followed by the exponential growth of the polymers
to form long fibrils that misfold and accumulate in the damaged cells.
Therefore, detection of soluble misfolded αSyn oligomers in biological fluids would
represent a good strategy for biochemical diagnosis of PD. In spite of
identifying biochemical markers for PD, there is an absence of an accepted and
validated surrogate biomarker.
Therefore, efforts have been made
for the availability of a sensitive, specific, and noninvasive biochemical
marker for the diagnosis and monitoring of disease progression as well as early
identification of neurodegenerative diseases. In this direction, Soto and his
team have provided a novel procedure for specific detection of αSyn aggregates
in biological fluids of PD and other synuclein aggregation disorders. The
findings of the seeding-nucleation process for detecting the misfolded
oligomers of αSyn were published in JAMA Neurology, 2016.
Over the past, seeding protein
misfolding cyclic amplification (PMCA) has been extensively used for
understanding biology, mechanisms and ultrasensitive detection of prions
(infectious protein particles) in biological fluids.
In the present study,
researchers have adapted PMCA for the highly sensitive detection of αSyn
aggregates (αSyn-PMCA) in cerebrospinal fluid (CSF) samples of those affected
by PD and those of individuals with other neurologic diseases from 2013 to
2015. The study subjects obtained from Japan and Germany constituted CSF
samples of patients suffering from PD (n=76) and controls affected by other
neurologic disorders (n = 65), neurodegenerative diseases (n = 18), and Alzheimer
disease (n = 14). The αSyn-PMCA assays revealed the kinetics of αSyn
aggregation which was correlated with disease severity. Interestingly,
evaluation of synthetic αSyn aggregates showed that αSyn-PMCA enabled the
detection of αSyn oligomers at low levels (0.1 pg/mL), indicating that the
αSyn-PMCA signal was directly proportional to the amount of αSyn oligomers
added to the reaction.
In addition, the blinded study of CSF samples correctly
identified PD patients with an overall 88.5% sensitivity and 96.9% specificity
from other neurological diseases. Also, the findings of the Japanese and German
cohort revealed αSyn-PMCA results were correlated with the severity of the
clinical symptoms of PD.
Therefore, a biochemical
diagnostic procedure is a useful tool in monitoring the progression of the
disease, providing targets for novel treatments and their potential mechanism
of action. In summary, PMCA is a platform technology which is employed to
detect the presence of misfolded aggregates of proteins circulating in the
biological fluids of those with neurodegenerative diseases. In addition
to the pathological confirmation of PD, the PMCA method’s ability to
differentiate PD αSyn from other synucleinopathies, and optimization of
blood-based αSyn-PMCA, would further optimize the clinical evaluation of PD.
Therefore, prion proteins combined with PMCA, Aβ-PMCA, and αSyn-PMCA along with
tau and TDP-43 aggregates would be a probable complete panel of tests for
screening and diagnosing neurodegenerative diseases as well as development of
patient-specific therapeutic interventions.
http://www.medicalnewsbulletin.com/biochemical-diagnosis-parkinsons-disease/
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