Cell-Free DNA Biomarkers in Neurodegenerative Disorders

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Highlights:

• Parkinson's disease and multiple system atrophy are neurodegenerative disorders that are characterized by motor impairment
• Mitochondrial and cell loss are the common pathological features found in these conditions
• Cell-free DNA biomarkers act as a non-invasive method to monitor cell damage and mitochondrial dysfunction

Parkinson's disease and multiple system atrophy (MSA) are neurodegenerative disorders that show progressive movement impairment. They differ in their pathological features (1^✔).

Parkinson's disease is characterized by the loss of dopaminergic neurons in the substantia nigra or black nucleus of the midbrain. While MSA involves widespread degeneration of the dopaminergic and olivary-cerebellar pathways.

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Both conditions show similar symptoms like motor impairment but distinct underlying pathophysiologies make diagnosis challenging. Mitochondrial and cell loss are common pathological features found in these conditions.

Role of Cell-free DNA as Biomarkers

Cell-free DNA has emerged as a non-invasive biomarker for various diseases including neurodegenerative disease. Cell-free DNA including circulating nuclear DNA (cf-nDNA) and mitochondrial DNA (cf-mtDNA) can be assessed to differentiate these conditions.

Plasma cf-nDNA and cf-mtDNA can be used to find the extent of cellular damage and mitochondrial dysfunction which are key features of Parkinson's disease and MSA.

Cell-free DNA Biomarkers can Track Symptoms

Plasma samples can examine specific biomarkers related to cell damage and mitochondrial dysfunction. The cf-nDNA levels were assessed to detect and quantify specific DNA sequences.

The cf-mtDNA copy number is the amount of mitochondrial DNA present in plasma that indicates cell damage or stress. cf-mtDNA deletion levels measure the number of damaged or missing parts in the mitochondrial DNA. High deletion levels indicate mitochondrial dysfunction.

Levels of cf-nDNA, cf-mtDNA and cf-mtDNA deletions are similar in both Parkinson's disease and multiple system atrophy and healthy persons. This shows that these biomarkers cannot be used as standalone diagnostic tests.

Higher levels of cf-nDNA are linked to more anxiety and lower cf-mtDNA levels are associated with constipation in PD patients. This explains that these biomarkers are linked to certain symptoms.

In MSA patients worsened movement problems and thinking abilities are linked to higher cf-nDNA levels indicating that it plays a role in brain functioning issues.

The biomarkers can not accurately predict who has PD or MSA, limiting its use in diagnosis. They may not help distinguish PD from MSA but they can be used to monitor symptom progression.

Larger studies are needed to prove that the changes in the biomarkers can match disease progression. Combining cf-nDNA and cf-mtDNA with other diagnostic markers might help improve diagnosis or understanding of the diseases.

Future research could also explore therapies targeting mitochondrial dysfunction or protecting brain cells to slow or prevent disease progression.

Reference:

1. Probing the diagnostic values of plasma cf-nDNA and cf-mtDNA for Parkinson's disease and multiple system atrophy - (https:www.frontiersin.org/journals/neuroscience/articles/10.3389/fnins.2024.1488820/abstract)

Source: Medindia

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