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A High Throughput, Multiplexed and Targeted Proteomic CSF Assay to Quantify Neurodegenerative Biomarkers and Apolipoprotein E Isoforms Status
Published on: October 20, 2016
Targeted metabolomic profiling of cerebrospinal fluid from patients with progressive multifocal leukoencephalopathy
Yi Luo1, Nora Möhn1, Amani Al-Mekhlafi2
1Department of Neurology, Hannover Medical School, Hannover, Germany.
Abstract:
Progressive multifocal leukoencephalopathy (PML), caused by JC polyomavirus, is a demyelinating disease of the central nervous system that primarily affects oligodendrocytes. It can cause significant morbidity and mortality. An early diagnosis is of high relevance as timely immune reconstitution is essential. However, diagnosis can be challenging if virus detection via cerebrospinal fluid (CSF) PCR remains negative. Hence, identifying CSF biomarkers for this disease is of crucial importance. We applied a targeted metabolomic screen to CSF from 23 PML patients and eight normal pressure hydrocephalus (NPH) patients as controls. Out of 188 potentially detectable metabolites, 48 (13 amino acids, 4 biogenic amines, 1 acylcarnitine, 21 phosphatidylcholines, 8 sphingolipids, and the sum of hexoses) passed the quality screen and were included in the analyses. Even though there was a tendency towards lower concentrations in PML (mostly of phosphatidylcholines and sphingomyelins), none of the differences between PML and controls in individual metabolite concentrations reached statistical significance (lowest p = 0.104) and there were no potential diagnostic biomarkers (highest area under the ROC curve 0.68). Thus, CSF metabolite changes in PML are likely subtle and possibly larger group sizes and broader metabolite screens are needed to identify potential CSF metabolite biomarkers for PML.
Insights
Diagnosing progressive multifocal leukoencephalopathy (PML) is challenging. This study found no significant cerebrospinal fluid (CSF) metabolite biomarkers in PML patients, suggesting subtle changes require larger studies.
Area of Science:
- Neuroscience
- Infectious Diseases
- Biochemistry
Background:
- Progressive multifocal leukoencephalopathy (PML) is a severe demyelinating disease of the central nervous system caused by JC polyomavirus.
- Early diagnosis of PML is critical for timely immune reconstitution and improved patient outcomes.
- Current diagnostic methods, such as CSF PCR, can be negative, highlighting the need for alternative biomarkers.
Purpose of the Study:
- To investigate cerebrospinal fluid (CSF) metabolite profiles for potential diagnostic biomarkers in PML.
- To compare metabolite concentrations between PML patients and healthy controls.
Main Methods:
- A targeted metabolomic screen was performed on CSF samples from 23 PML patients and 8 controls (normal pressure hydrocephalus).
- 48 metabolites, including amino acids, biogenic amines, acylcarnitine, phosphatidylcholines, sphingolipids, and hexoses, were analyzed.
- Statistical analysis was used to compare metabolite concentrations between groups.
Main Results:
- No individual metabolite concentrations showed statistically significant differences between PML patients and controls.
- Phosphatidylcholines and sphingomyelins showed a trend towards lower concentrations in PML patients.
- The highest area under the ROC curve for any metabolite was 0.68, indicating no reliable diagnostic biomarker was identified.
Conclusions:
- Cerebrospinal fluid (CSF) metabolite changes in PML may be subtle.
- Larger patient cohorts and broader metabolomic screening approaches are likely necessary to identify potential CSF metabolite biomarkers for PML.
