Abstract
INTRODUCTION Understanding 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.
METHODS We 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.
RESULTS We 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.
DISCUSSION Cross-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.
Authors and Affiliations
Isabelle Kowal¹, Sonja W. Scholz²˒³, Jacob Epstein¹, Bryan J. Traynor³˒⁴, Laura E. Danielian², Ying Hao¹, Jody Crook², Ziyi Li¹˒⁵, Katelyn Porter², Brian Sellers⁶, Thomas J. Langowski⁶, Marisa N. Denkinger⁷˒⁸, Nicholas J. Ashton⁸, Kendall Van Keuren-Jensen¹˒⁹, Mark R. Cookson¹, Justin Y. Kwan², Yue A. Qi¹˒¹¹*, and Allison Snyder²˒¹⁰˒¹¹*
¹ Center for Alzheimer’s and Related Dementias (CARD), National Institute on Aging and National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
² National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA
³ Department of Neurology, Johns Hopkins University Medical Center, Baltimore, MD, USA
⁴ National Institute on Aging, National Institutes of Health, Bethesda, MD, USA
⁵ DataTecnica LLC, Washington, DC, USA
⁶ NIH Center for Human Immunology, National Institutes of Health, Bethesda, MD, USA
⁷ Department of Psychiatry and Neurochemistry, Institute of Neuroscience & Physiology, the Sahlgrenska Academy at the University of Gothenburg, Mölndal, Sweden
⁸ Banner Sun Health Research Institute, Sun City, AZ, USA
⁹ Translational Genomics Research Institute, Phoenix, AZ, USA
¹⁰ Frontotemporal Degeneration Center, University of Pennsylvania, Philadelphia, PA, USA
¹¹ Yue A. Qi and Allison Snyder contributed equally.
* Corresponding authors: Yue A. Qi and Allison Snyder.