Distinct protein profiles in cord blood plasma of children with autism spectrum disorder

Autism spectrum disorder (ASD) has a genetic origin in approximately 30% of cases, while the remaining causes are primarily linked to epigenetic and non-genetic factors. This study aims to identify potential non-genetic causes contributing to ASD by investigating the underlying cellular mechanisms through proteomic analysis. Extracellular vesicles (EVs) mediate cellular communication and are linked to brain development disorders. Here, we utilize mass-spectrometry-based proteomic analysis of EVs derived from umbilical cord blood plasma collected from 30 children diagnosed with non-syndromic ASD and 30 neurotypical controls. The analysis identified 565 proteins with significantly different expression levels, most of which were more abundant in the ASD group. Notably, the protein expression variances were markedly lower in the ASD group, suggesting a similar cellular activity. Differentially expressed proteins were clustered using String software into 3 groups: mitochondria, endoplasmic reticulum (ER), and a mixture of immune and cytoskeletal proteins. Further statistical analysis identified 11 strongly predictive ASD proteins, while the Human Protein Atlas recognized an additional 13 brain-specific proteins. A portion of these 24 proteins was associated with synaptogenesis and myelination. These findings suggest that, despite diverse etiologies, ASD may converge on a common final pathway involving mitochondrial and ER dysfunction, resulting in abnormal synaptogenesis. This study presents the first unbiased proteomic analysis of exosomal proteins aimed at determining whether neurodevelopmental disruptions linked to ASD originate prenatally or postnatally.