Neurodevelopmental Impact of Advanced Glycation End Products in Children with Autism Spectrum Disorder

Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder with compromised prognosis and treatment. Current research has shown that along with genetic factors, maternal health, environmental exposures, and epigenetic modifiers play a critical pathogenic role. Emerging scientific evidence reveals the significant impact of increased advanced glycation end products (AGEs) in impairing pediatric brain development that may contribute to ASD by inducing neuroinflammation and oxidative stress through activation of the receptor for AGEs (RAGE) signaling in neuronal cells. Accumulation of AGEs has been shown to disrupt the blood-brain barrier (BBB) integrity, which is crucial for protecting the developing brain from harmful substances, as well as interfering with the vascular function and blood flow, affecting brain maturation, and inducing neuroendocrine dysregulation. In this review, we describe the impact of AGEs on pediatric brain development and synaptic plasticity, critical for learning and memory, as well as their input in exacerbating neuroinflammation through microglia activation, contributing to the development of autism-related neuropathology. We further discuss the diagnostic and patients' stratification potential of specific AGE types as well as current interventions to reduce their exposure and tissue accumulation, mitigating their harmful effects to support a better neurodevelopmental outcome in children.