# Reproducibility and Other Issues in CSF proteomics to identify early biomarkers for neurodegenerative disease

**URL:** <https://scientistsolutions.discourse.group/t/reproducibility-and-other-issues-in-csf-proteomics-to-identify-early-biomarkers-for-neurodegenerative-disease/1233>\
**Category:** Mass Spectrometry\
**Created:** [December 17, 2025, 8:11pm UTC](https://scientistsolutions.discourse.group/t/reproducibility-and-other-issues-in-csf-proteomics-to-identify-early-biomarkers-for-neurodegenerative-disease/1233 "2025-12-17T20:11:05Z")\
**Posts on this page:** 1\
**Page:** 1

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**Author:** ![Biographix](https://avatars.discourse-cdn.com/v4/letter/b/b9bd4f/32.png) [@Biographix](https://scientistsolutions.discourse.group/u/Biographix)\
**Post date:** [December 17, 2025, 8:11pm UTC](https://scientistsolutions.discourse.group/t/reproducibility-and-other-issues-in-csf-proteomics-to-identify-early-biomarkers-for-neurodegenerative-disease/1233/1 "2025-12-17T20:11:05Z")

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We are performing CSF proteomics to identify early biomarkers for neurodegenerative disease using LC–MS/MS. Despite following standardized protocols, we are facing reproducibility and biological interpretation issues.

1. **Poor overlap of differentially expressed proteins** between discovery and validation cohorts, even when using targeted MS.
2. **Ambiguous biological relevance** , where statistically significant proteins lack clear mechanistic links to CNS pathology

Would alternative approaches (e.g., DIA-MS, extracellular vesicle enrichment, PTM-focused proteomics, or single-molecule methods) provide more reproducible insights?

What minimum standards should be enforced for CSF handling to improve cross-study comparability?

Thanks in advance