Disentangling the role of tau pathology in autism spectrum disorders

Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficient social interaction, altered communication, and repetitive, stereotyped behaviors. Pathologically, ASD is characterized by abnormal brain development, including dendritic spine and axonal alterations, which are both associated with synaptic plasticity disturbances. Microtubules (MT) and microtubule-associated proteins (MAPs) are critical in regulating brain development by the neuronal cytoskeleton and synaptic formation. Tau is a neuronal MAP protein in which pathological posttranslational modifications (PTMs) are involved in the pathogenesis of neurodegenerative diseases (NDs), including Alzheimer's disease (AD). In this context, accumulative evidence suggests that tau is altered in mouse models and human patients of ASD. Toxic tau modifications like hyperphosphorylation, a disruptor of MTs dynamics, produced alterations in ASD, suggesting that the imbalance of this protein may contribute to neurodevelopmental deficiencies produced during ASD. In this systematic review, we revised essential evidence suggesting that the dysregulation of cytoskeletal components produced by tau pathology could play a crucial role in the pathological and behavioral changes produced in ASD. Finally, we will focus on discussing how the presence of tau pathology in ASD contributes to brain development impairment and whether pathological forms of tau could be suggested as a novel biomedical strategy to support the diagnosis of this disorder.