Researchers Identify Potential Biomarker for Autism

Researchers Identify Potential Biomarker for Autism

A brain protein has been identified that is present in low levels in patients with autism, which could potentially be used as a biomarker to help with the diagnosis of the disorder.

Researchers at Northwestern Medicine were investigating the link between autism and epilepsy in children and analyzed the cerebrospinal fluid of children with autism and epilepsy, and also analyzed the cerebrospinal fluid in mouse models. They discovered a brain protein in the cerebrospinal fluid that quietens overactive brain cells, which is only present in low levels in children with autism.

“Although many neuronal membrane proteins undergo proteolytic cleavage, little is known about the biological significance of neuronal ectodomain shedding (ES). Here, we show that the neuronal sheddome is detectable in human cerebrospinal fluid (hCSF) and is enriched in neurodevelopmental disorder (NDD) risk factors,” explained the researchers in the paper. “Among shed synaptic proteins is the ectodomain of CNTNAP2 (CNTNAP2-ecto), a prominent NDD risk factor. CNTNAP2 undergoes activity-dependent ES via MMP9 (matrix metalloprotease 9), and CNTNAP2-ecto levels are reduced in the hCSF of individuals with autism spectrum disorder.”

CNTNAP2 can be synthesized in the lab and could be injected into the cerebrospinal fluid, from where it will enter the brain. In addition to measuring levels to aid diagnosis of autism, CNTNAP2 could potentially serve as a treatment for epilepsy in children.

“Our data underscore the promise of sheddome analysis in discovering neurobiological mechanisms, provide insight into the biology of ES and its relationship with the CSF, and reveal a mechanism of regulation of Ca2+ homeostasis and neuronal network synchrony by a shed ectodomain,” said the researchers.

You can read more about the study in the paper – Shed CNTNAP2 ectodomain is detectable in CSF and regulates Ca2+ homeostasis and network synchrony via PMCA2/ATP2B2 – which was recently published in Neuron. DOI: 10.1016/j.neuron.2021.11.025