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Published on: October 13, 2016
Leukocyte Derived Microvesicles as Disease Progression Biomarkers in Slow Progressing Amyotrophic Lateral Sclerosis
Daisy Sproviero1, Sabrina La Salvia1, Federico Colombo2
1Genomic and Post-Genomic Center, IRCCS Mondino Foundation, Pavia, Italy.
Abstract:
The lack of biomarkers in Amyotrophic Lateral Sclerosis (ALS) makes it difficult to determine the stage of the disease in patients and, therefore, it delays therapeutic trials. Microvesicles (MVs) are possible biomarkers implicated in physiological and pathological functions, however, their role in ALS remains unclear. We investigated whether plasma derived microvesicles could be overrepresented in a group of 40 patients affected by ALS compared to 28 Alzheimer's Disease (AD) patients and 36 healthy volunteers. Leukocyte derived MVs (LMVs) compared to endothelial, platelet, erythrocyte derived MVs, were mostly present in ALS patients compared to AD patients and healthy donors. Correlation analysis corrected for the presence of confounding variables (riluzole, age at onset, site of onset, gender) was tested between PRL (Progression Rate at the Last visit) and LMVs, and a statistically significant value was found (Pearson partial correlation r = 0.407, p = 0.006). We also investigated SOD1, TDP-43 intravesicular protein level in LMVs. Misfolded SOD1 was selectively transported by LMVs and its protein level was associated with the percentage of LMVs in slow progressing patients (r = 0.545, p = 0.033). Our preliminary findings suggest that LMVs are upregulated in ALS patients and they can be considered possible markers of disease progression.
Insights
Leukocyte-derived microvesicles (LMVs) are elevated in Amyotrophic Lateral Sclerosis (ALS) patients. Increased LMVs correlate with disease progression and may serve as potential biomarkers for ALS.
Area of Science:
- Neuroscience
- Biomarker Discovery
- Cell Biology
Background:
- Amyotrophic Lateral Sclerosis (ALS) lacks reliable biomarkers, hindering diagnosis and therapeutic development.
- Microvesicles (MVs), implicated in various physiological and pathological processes, have an unclear role in ALS.
- Plasma-derived MVs are investigated as potential diagnostic and prognostic indicators in neurodegenerative diseases.
Purpose of the Study:
- To determine if plasma-derived microvesicles are overrepresented in ALS patients compared to Alzheimer's Disease (AD) patients and healthy controls.
- To investigate the correlation between leukocyte-derived microvesicles (LMVs) and disease progression rate in ALS.
- To analyze the intravesicular levels of SOD1 and TDP-43 within LMVs and their association with disease characteristics.
Main Methods:
- Quantification of plasma-derived microvesicles (MVs) including leukocyte-derived MVs (LMVs) in 40 ALS patients, 28 AD patients, and 36 healthy volunteers.
- Correlation analysis between LMVs and Progression Rate at the Last visit (PRL), adjusted for confounding factors.
- Assessment of intravesicular SOD1 and TDP-43 protein levels in LMVs.
Main Results:
- LMVs were significantly more abundant in ALS patients compared to AD patients and healthy donors.
- A statistically significant positive correlation was found between LMVs and disease progression rate (Pearson partial correlation r = 0.407, p = 0.006).
- Misfolded SOD1 was selectively transported by LMVs, and its level correlated with LMVs in slow-progressing patients (r = 0.545, p = 0.033).
Conclusions:
- Leukocyte-derived microvesicles (LMVs) are upregulated in the plasma of ALS patients.
- LMVs show potential as biomarkers for tracking disease progression in Amyotrophic Lateral Sclerosis.
- Further research is warranted to validate LMVs as reliable biomarkers for ALS management and therapeutic trials.
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