Disentangling the role of tau pathology in autism spectrum disorders.

This review looked at how a brain protein called tau might be involved in autism. Tau normally helps brain cells maintain their structure, but when it becomes damaged, it can cause problems with brain development. The researchers found evidence that tau protein is altered in people with autism and in autism research models. These tau changes might contribute to the brain differences seen in autism and could potentially be used as a way to help diagnose autism in the future.

This systematic review examines the role of tau protein pathology in autism spectrum disorders (ASD). Tau is a neuronal protein that, when abnormally modified, contributes to neurodegenerative diseases like Alzheimer's. The authors reviewed evidence suggesting that tau alterations occur in both mouse models and human patients with ASD. Pathological tau modifications, particularly hyperphosphorylation, disrupt microtubule dynamics and may contribute to the synaptic plasticity disturbances, dendritic spine abnormalities, and axonal alterations characteristic of ASD.

The review proposes that tau pathology could contribute to neurodevelopmental deficiencies in ASD and suggests that pathological tau forms might serve as potential biomarkers for ASD diagnosis, representing a novel biomedical approach to support clinical assessment.

This research suggests tau protein assessment could become a biomedical tool for ASD diagnosis. However, translation to clinical practice requires validation studies. The findings may inform future therapeutic targets focused on tau pathology, though interventions targeting tau in ASD remain theoretical. Clinicians should note this represents early-stage research requiring further investigation.

The abstract does not specify the number of studies included, search strategy, or quality assessment criteria used in this systematic review. Sample sizes and methodological details of included studies are not provided, limiting assessment of the evidence quality.

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.