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A dual proteomics analysis of paired cerebrospinal fluid and plasma from patients with neurodegenerative diseases

  • I. Kowal
  • S. W. Scholz
  • J. Epstein
  • B. J. Traynor
  • L. E. Danielian
  • Y. Hao
  • J. Crook
  • Z. Li
  • K. Porter
  • B. Sellers
  • T. J. Langowski
  • M. N. Denkinger
6 more authors
  • N. J. Ashton
  • K. Van Keuron-Jensen
  • M. R. Cookson
  • J. Y. Kwan
  • Y. A. A. Qi1
  • A. Snyder
  1. 1Center for Alzheimer's and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institute
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Abstract

INTRODUCTIONUnderstanding concordance across biofluids and platforms is critical for understanding neurodegenerative biomarkers results and translating them into clinical use; yet systematic comparisons remain limited. To address this gap, we performed large-scale proteomic profiling of patient-paired plasma and CSF to characterize cross-modal relationships.

METHODSWe profiled paired plasma and CSF from 67 individuals using SomaScan 11K and NULISAseq CNS panels. Disease severity was assessed with the CDR+NACC FTLD-M Global Score.

RESULTSWe identified 269 SomaScan and 18 NULISA proteins with significant cross-biofluid correlation. Cross-platform concordance within biofluids was strong. NEFL, NPTX2, TREM2, and CHIT1 demonstrated consistent cross-platform agreement. Associations with disease severity were compartment-specific, with decreased NPTX2 in CSF, increased NEFL and GFAP in plasma, and decreased TREM2 across biofluids.

DISCUSSIONCross-platform consistency supports biomarker robustness, while limited cross-biofluid concordance highlights compartmental biology. Given additional clinical correlations despite varying underlying pathology, these findings may point to shared neurodegenerative disorder pathways.

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Cite

BibTeXRIS
BibTeX
@misc{kowal2026dual,
  title = {{A dual proteomics analysis of paired cerebrospinal fluid and plasma from patients with neurodegenerative diseases}},
  author = {I. Kowal and S. W. Scholz and J. Epstein and B. J. Traynor and L. E. Danielian and Y. Hao and J. Crook and Z. Li and K. Porter and B. Sellers and T. J. Langowski and M. N. Denkinger and N. J. Ashton and K. Van Keuron-Jensen and M. R. Cookson and J. Y. Kwan and Y. A. A. Qi and A. Snyder},
  howpublished = {medRxiv},
  year = {2026},
  month = sep,
  doi = {10.64898/2026.09.02.26361977},
  url = {https://www.medrxiv.org/content/10.64898/2026.09.02.26361977v1},
  note = {CC0},
}
RIS
TY  - UNPB
TI  - A dual proteomics analysis of paired cerebrospinal fluid and plasma from patients with neurodegenerative diseases
AU  - I. Kowal
AU  - S. W. Scholz
AU  - J. Epstein
AU  - B. J. Traynor
AU  - L. E. Danielian
AU  - Y. Hao
AU  - J. Crook
AU  - Z. Li
AU  - K. Porter
AU  - B. Sellers
AU  - T. J. Langowski
AU  - M. N. Denkinger
AU  - N. J. Ashton
AU  - K. Van Keuron-Jensen
AU  - M. R. Cookson
AU  - J. Y. Kwan
AU  - Y. A. A. Qi
AU  - A. Snyder
PY  - 2026
DA  - 2026/09/02
PB  - medRxiv
DO  - 10.64898/2026.09.02.26361977
UR  - https://www.medrxiv.org/content/10.64898/2026.09.02.26361977v1
AB  - INTRODUCTIONUnderstanding concordance across biofluids and platforms is critical for understanding neurodegenerative biomarkers results and translating them into clinical use; yet systematic comparisons remain limited. To address this gap, we performed large-scale proteomic profiling of patient-paired plasma and CSF to characterize cross-modal relationships.  METHODSWe profiled paired plasma and CSF from 67 individuals using SomaScan 11K and NULISAseq CNS panels. Disease severity was assessed with the CDR+NACC FTLD-M Global Score.  RESULTSWe identified 269 SomaScan and 18 NULISA proteins with significant cross-biofluid correlation. Cross-platform concordance within biofluids was strong. NEFL, NPTX2, TREM2, and CHIT1 demonstrated consistent cross-platform agreement. Associations with disease severity were compartment-specific, with decreased NPTX2 in CSF, increased NEFL and GFAP in plasma, and decreased TREM2 across biofluids.  DISCUSSIONCross-platform consistency supports biomarker robustness, while limited cross-biofluid concordance highlights compartmental biology. Given additional clinical correlations despite varying underlying pathology, these findings may point to shared neurodegenerative disorder pathways.
ER  -