Challenges to Diagnosing Parkinsonian Disorders
Parkinsonian disorders, commonly referred to as parkinsonism, are a group of neurological conditions characterized by motor symptoms like those observed in Parkinson's disease (PD). These disorders share common features such as bradykinesia (slowness of movement), muscle rigidity, resting tremors, and postural instability.
Parkinson's disease is the most recognizable form of parkinsonism. It is characterized by a progressive loss of dopamine-producing neurons in the substantia nigra of the brain. This results in the characteristic motor symptoms associated with PD.
However, there are several other parkinsonian disorders. These include dementia with Lewy Bodies (DLB), Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), and Corticobasal Syndrome (CBS).
These disorders impose a growing burden on patients, caregivers, and society, particularly because of increasing life expectancy. Aging is the primary risk factor for many neurodegenerative disorders. These conditions share motor symptoms, and also exhibit distinct clinical features, progression patterns, and underlying causes.
Parkinsonian diseases are often misdiagnosed because symptoms overlap with other conditions. This makes diagnosis challenging, and clinicians primarily rely on clinical criteria. The lack of early, specific biomarkers of disease adds to diagnostic difficulties. Current diagnostic tools are not sensitive enough to diagnose these disorders until many neurons are lost.
Ongoing research by groups like Aligning Science Across Parkinson's (ASAP) and the Michael J. Fox Foundation is working toward a better understanding of the biological mechanisms of parkinsonism. Genetic studies and screenings are mapping clinically relevant PD genes and providing genetic counseling for affected individuals. However, additional insights are still necessary to delineate between Parkinsonian disorders.
Psomagen was recently pleased to announce our participation in sequencing the genomes of a global cohort of 80,000 PD patients and research participants, in conjunction with the Global Parkinson's Genetics Program (GP2). This sequencing effort works toward GP2’s aim to use genetic knowledge to accelerate the path to the development and deployment of therapeutic strategies for Parkinson’s Disease.You can read the full press release here.
Identifying Biomarkers for Neurodegenerative Disease
To improve diagnosis, a group of researchers from Sweden and Italy focused on identifying potential biomarkers for Parkinsonian disorders. Their focus included Lewy body disease (LBD), PD, DLB, and atypical Parkinsonian syndromes like MSA, PSP, and CBS. Their work explores cerebrospinal fluid (CSF) as a source of biomarkers for neurodegenerative disorders, similar to the use of CSF biomarkers in Alzheimer's disease.
With the Olink Explore 3072 platform, they determined the CSF concentrations of close to 3,000 proteins in 428 samples from the Swedish BioFINDER 2 cohort. These samples included 347 controls and 81 LBD patients. This immunoassay makes use of Olink PEA technology, which provides high-throughput, multiplex assays with small sample volumes.
Data was subjected to differential expression analysis on key biomarkers. This analysis identified a potential and unique biomarker for DLB and atypical parkinsonism. DOPA decarboxylase (DDC), which plays a crucial role in dopamine production, was elevated in patients with LBD and atypical PS.
Elevated DDC was present even in preclinical stages, making it a promising early biomarker. The combination of DDC with specific α-synuclein assays could improve the differentiation of LBD from atypical PS.
Furthermore, the study demonstrates that DDC levels are also elevated in the plasma. This makes plasma a candidate diagnostic tool. The research emphasizes the importance of replicating these findings in additional cohorts and conducting longitudinal studies to assess the clinical value of DDC as a biomarker over time.
Overall, the study suggests that DDC holds promise as a biomarker for the early detection and differentiation of Parkinsonian disorders. This addresses a critical need for more effective, accurate, and accessible diagnostic markers.
Interested in this research? Take a look at the full article, DOPA decarboxylase is an emerging biomarker for Parkinsonian disorders including preclinical Lewy body disease.
