Serum MAP1A as a Potential Biomarker for Autism Spectrum Disorder

초록

Highlights What are the main findings? Synapse-related genes dysregulated in an ASD model brain were systematically screened and cross-validated with human serum proteomic data. MAP1A was identified as a translational blood-based biomarker candidate showing consistent alteration across animal and human datasets. What are the implications of the main findings? These findings suggest the feasibility of using peripheral blood biomarkers for the objective diagnosis of autism spectrum disorder. The cross-species brain-to-blood validation strategy provides a practical framework for discovering clinically translatable ASD biomarkers.Highlights What are the main findings? Synapse-related genes dysregulated in an ASD model brain were systematically screened and cross-validated with human serum proteomic data. MAP1A was identified as a translational blood-based biomarker candidate showing consistent alteration across animal and human datasets. What are the implications of the main findings? These findings suggest the feasibility of using peripheral blood biomarkers for the objective diagnosis of autism spectrum disorder. The cross-species brain-to-blood validation strategy provides a practical framework for discovering clinically translatable ASD biomarkers.Abstract Background/Objectives: Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental condition currently diagnosed through subjective behavioral assessments. Objective blood-based biomarkers are needed to enable earlier and more accurate identification. In this study, we aimed to identify synapse-related biomarkers associated with ASD and evaluate their potential as serum-based indicators. Methods: RNA sequencing was performed on the cerebellum, hippocampus, and cerebral cortex of a valproic acid-induced rat model of ASD to identify differentially expressed genes (DEGs). Functional enrichment analyses, including Gene Ontology and Kyoto Encyclopedia of Genes and Genomes, were conducted to explore associated pathways. Synapse-related hub genes were selected by comparison with the SFARI autism gene database, and the serum expression of candidate proteins was assessed using Western blotting. Results: A total of 692, 813, and 1059 DEGs were identified in the cerebellum, hippocampus, and cortex, respectively. Enrichment analyses highlighted dendrite development, postsynaptic density, and glutamatergic synapse pathways as significantly affected. Six synaptic hub genes were prioritized, among which serum MAP1A expression was significantly elevated in the ASD rats. Conclusions: These findings suggest that serum MAP1A may represent a potential biomarker reflecting synaptic abnormalities in ASD. Further validation in human cohorts and integration into a multi-marker framework are warranted to account for the heterogeneity of ASD.

키워드