Impaired aggrephagy,abnormal vesicular trafficking and cellular stress, lead to protein aggregation,neurodegeneration and synaptic dysfunction in cerebellar vermis of children and adults with idiopathic autism

Autism spectrum disorder (ASD) is a debilitating neurodevelopmental disorder with genetic and environmental etiologies involving several brain areas exhibiting abnormalities of cognition and social behavior. Previous work showed involvement of synaptic abnormalities in dorsolateral prefrontal cortex. We hypothesized whether similar synaptic proteins were involved in pathology of cerebellar vermis of children and adults with ASD. Subcellular fractions of synaptosomes from cerebellar vermal cortices of age-, brain area-, and postmortem-interval- matched samples from children and adults with idiopathic ASD vs. controls were subjected to HPLC-tandem mass spectrometry. Analysis of proteomic data in cerebellar vermis showed common and distinct effects of ASD on protein- and pathway-enrichment for children vs. adults.