# Serum Proteomics Reveals Diagnostic Biomarkers and Molecular Pathways in Cerebral Palsy

## TL;DR

This study identifies blood protein patterns that can help diagnose cerebral palsy early and reveals molecular pathways involved in the condition.

## Contribution

A 10-protein diagnostic panel and insights into genetic and environmental factors in cerebral palsy pathogenesis are newly presented.

## Key findings

- A 10-protein multi-marker panel was developed and validated for diagnosing cerebral palsy.
- CP patients with pathogenic variants showed downregulation of synaptic and calcium signaling pathways.
- Low birth weight and gestational age were linked to lipid metabolism disruptions in proteomic data.

## Abstract

Cerebral palsy (CP), a prevalent non-progressive neurological disorder in children, lacks reliable biomarkers for early diagnosis, and its molecular mechanisms remain poorly understood. In this study, we conducted serum proteomic profiling of 346 CP patients and 190 healthy controls and developed a 10-protein multi-marker panel for application in diagnosis of CP. The panel was further validated in an independent CP cohort using an orthogonal method, enzyme-linked immunosorbent assay (ELISA). By integrating serum proteomic data with whole-exome sequencing (WES) results, we found that CP patients carrying pathogenic variants exhibited downregulation of synaptic and calcium signaling pathways at the protein level. We also explored the impact of clinical risk factors on the proteome, identifying disruptions in lipid metabolism associated with low birth weight and low gestational age. Additionally, we found a positive correlation between Immunoglobulin Heavy Variable (IGHV) families and higher Gross Motor Function Classification System (GMFCS) levels. Overall, our study provides a valuable tool for early CP diagnosis that complements standard clinical and genomic assessments, and suggests potential molecular mechanisms associated with CP pathogenesis, highlighting the interplay among genetic, environmental, and protein network factors.

Cerebral palsy lacks reliable biomarkers for early and accurate diagnosis. Here, the authors show serum proteomic signatures of disease and develop a multi-biomarker diagnostic model.