Variability in CSF Protein Levels Across Neurodegenerative Diseases
Author Information
Author(s): Mravinacová Sára, Bergström Sofia, Olofsson Jennie, de San José Nerea Gómez, Anderl-Straub Sarah, Diehl-Schmid Janine, Fassbender Klaus, Fliessbach Klaus, Jahn Holger, Kornhuber Johannes, Landwehrmeyer G. Bernhard, Lauer Martin, Levin Johannes, Ludolph Albert C., Prudlo Johannes, Schneider Anja, Schroeter Matthias L., Wiltfang Jens, Steinacker Petra, Otto Markus, Nilsson Peter, Månberg Anna
Primary Institution: Department of Protein Science, SciLifeLab, KTH Royal Institute of Technology, Stockholm, Sweden
Hypothesis
How does inter-individual variability in cerebrospinal fluid (CSF) protein levels affect the diagnostic utility of biomarkers for neurodegenerative diseases?
Conclusion
Adjusting for inter-individual variability in CSF protein levels significantly enhances the association of these proteins with neurodegenerative diseases and improves their diagnostic performance.
Supporting Evidence
- Adjusting for median CSF levels of brain-derived proteins increases the diagnostic accuracy of proteins previously identified as altered in CSF.
- Two proteins—neurofilament medium and myelin basic protein—showed increased levels in ALS compared to other diseases.
- Neurogranin showed a specific increase in Alzheimer's disease.
- Many CSF protein alterations are shared across multiple neurodegenerative conditions, suggesting common underlying mechanisms.
- Using protein pairs with opposite alterations can enhance diagnostic performance.
Takeaway
This study shows that the levels of certain proteins in the fluid around our brain can vary a lot between people, and this can make it hard to tell if someone has a brain disease. By adjusting for these differences, we can get better at diagnosing these diseases.
Methodology
The study measured levels of 69 proteins in cerebrospinal fluid from 499 individuals with various neurodegenerative disorders and healthy controls using antibody-based suspension bead array technology.
Potential Biases
Potential bias due to the limited number of healthy controls and the pre-selection of proteins.
Limitations
The study has a limited number of measured proteins and lacks direct validation in an independent cohort.
Participant Demographics
Participants included patients with Alzheimer's disease, ALS, frontotemporal dementia, and healthy controls, with a mix of ages and genders.
Statistical Information
P-Value
p<0.05
Statistical Significance
p<0.05
Digital Object Identifier (DOI)
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