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Scientists discover new biomarker for autism in cerebrospinal fluid



Northwestern Medicine scientists have found a biomarker for a type of autism in the cerebrospinal fluid of patients, according to a study published in the journal Neuron.

The presence of this biomarker helps establish a link between autism and epilepsy, conditions that often coexist but whose connective mechanisms remain unknown, according to Peter Penzes, PhD, Professor Ruth and Evelyn Dunbar of Psychiatry and Human Sciences. behavior, professor of neuroscience and pharmacology, and lead author of the study.

“There is too much arousal and too little inhibition in the brain, which can impact both autism and epilepsy,” said Penzes, who is also director of the Center for Autism and Neurodevelopment. “This is the first report of a biomarker for autism in cerebrospinal fluid.”

Some autistic patients also suffer from epilepsy, especially patients whose autism is linked to mutations in the gene. CNTNAP2. This gene normally creates a cell adhesion protein that helps neurons connect to each other, but loss-of-function mutations have been linked to both autism and epilepsy.

In the present study, Penzes and colleagues analyzed the cerebrospinal fluid (CSF) of patients with autism and healthy controls, finding that patients with autism had fewer CNTNAP2 molecules floating freely in the CSF.

When CNTNAP2 floats freely, it functions more like a hormone than a cell glue, Penzes said, binding to neurons and reducing excitatory neurotransmissions. Therefore, CNTNAP2 may play a secondary role as a regulator of excitatory activity.

When the brain gets overly excited, CNTNAP2 is ruptured and attaches to brain cells like a kind of feedback switch. If you don’t have CNTNAP2, there is hyper-connectivity between neurons that can contribute to autism, and there is over-arousal of neurons that can lead to seizures. “

Peter Penzes, PhD, lead author of the study

The role of CNTNAP2 in regulating arousal was previously unknown, and indicates a possible future therapy in which CNTNAP2 could be given to patients to replace what their bodies cannot produce. However, its presence in CSF also opens up new possibilities as a biomarker, according to Penzes.

3D image of a neuron (green) and the CNTNAP2 protein floating away from the neuron.

“Measurements of behavioral health in people with autism could be very subjective, but if we can actually measure CNTNAP2 levels and correlate them with the effectiveness of a treatment, it could really improve implementation,” said Penzes.

Additionally, Penzes said he and his collaborators discovered other biomarkers associated with autism in CSF and that their study would be a priority for the future.

“Maybe these other factors could be used as biomarkers, and they could also tell us about similar unknown biological mechanisms, as CNTNAP2 did,” Penzes said.

Mr. Dolores Martin-de-Saavedra, PhD, assistant professor at Universidad Complutense (Madrid, Spain) and former postdoctoral fellow at Penzes Laboratory, was the lead author of the study. Jeffrey Savas, PhD, assistant professor in the Ken department of neurology and Ruth Davee, division of behavioral neurology, was co-author of the study.

This work was supported by grant NS100785 from the US National Institute of Neurological Disorders and Stroke and an Individual Biomedical Research Award from the Hartwell Foundation.