Low levels of protein in CSF linked to autism and epilepsy

Low levels of a “calming” brain protein may play a key role in autism and epilepsy, according to a new study. 

M. Dolores Martin-de-Saavedra and colleagues measured levels of a protein called CNTNAP2 in the cerebrospinal fluid (CSF) of individuals with autism as well as neurotypical controls. The researchers found that individuals with autism had fewer molecules of CNTNAP2 floating freely in the CSF. 

CNTNAP2 is best known for being a cellular adhesion protein that helps neurons connect to one another. However, the researchers say that when CNTNAP2 is floating freely, it functions more like a hormone than a cellular glue, binding to neurons and reducing excitatory neurotransmissions. Therefore, they say, CNTNAP2 may play a role as a regulator of excitatory activity. 

“When the brain is getting too excited, CNTNAP2 gets broken off and attaches to brain cells as a sort of feedback switch,” study coauthor Peter Penzes says. “If you don’t have CNTNAP2, there’s hyper-connectivity between neurons which can contribute to autism, and there’s excessive excitation of neurons which can lead to seizures.” 

The researchers say their study helps to establish a link between autism and epilepsy, two conditions that frequently co-occur. Additionally, they say, their findings could lead to treatments for individuals with autism and comorbid epilepsy.

Citations

“Shed CNTNAP2 ectodomain is detectable in CSF and regulates Ca2+ homeostasis and network synchrony via PMCA2/ATP2B2,” M. Dolores Martín-de-Saavedra, Marc Dos Santos, Lorenza Culotta, Olga Varea, Benjamin P. Spielman, Euan Parnell, Marc P. Forrest, Ruoqi Gao, Sehyoun Yoon, Emmarose McCoig, Hiba A. Jalloul, Kristoffer Myczek, Natalia Khalatyan, Elizabeth A. Hall, Liam S. Turk, Antonio SanzClemente, Davide Comoletti, Stefan F. Lichtenthaler, Jeffrey S. Burgdorf, Maria V. Barbolina, Jeffrey N. Savas, and Peter Penzes, Neuron, December 19, 2021 (online). Address: Peter Penzes, [email protected]. 

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“New autism biomarker discovered in cerebrospinal fluid,” news release, Will Doss, Northwestern University, December 17, 2021