Study reports tau anomalies in genetic condition causing autism, hints at possible treatment

Early in 2020, researchers reported that lowering levels of a protein called tau reduced symptoms in two mouse models of autism and epilepsy (see ARRI 2020, No. 2). Now, a new study by a separate group of scientists indicates that normalizing the effects of tau may ameliorate symptoms of another form of autism. 

Illana Gozes and colleagues, including first author Iris Grigg, found deposits of tau—a protein associated with Alzheimer’s disease—in postmortem tissue from the brain of a seven-year-old child with autism. The child had ADNP syndrome, a genetic disorder that causes autistic symptoms and other mental and physical symptoms and is responsible for about 0.2% of cases of autism overall. 

The researchers tested an experimental Alzheimer’s drug called NAP on nerve cells carrying an ADNP mutation similar to that seen in the child’s tissues. Gozes says, “NAP is actually a short active fragment of the normal ADNP protein. When we added NAP to the nerve cells carrying an ADNP mutation, the tau protein bound to the nerve cell skeleton properly, and the cells returned to normal function.” 

She adds, “The fact that NAP treatment has been successful in restoring the normal function of neuronal-like cell models with impaired ADNP raises hopes that it may be used as a remedy for ADNP syndrome and its severe implications, including autism. Moreover, because other genetic disorders related to autism are characterized by tau pathologies in the brain, we hope that those suffering from these syndromes will also be able to benefit from NAP treatment in the future.” 

To further understand the effects of the mutation that causes ADNP syndrome, the researchers extracted messenger RNA from the tissues of the deceased child and analyzed about 40 proteins in the child’s tissue encoded by the mRNA. In addition, they analyzed protein expression in white blood cells taken from three other children with the syndrome. The researchers found a variety of characteristics that were common to the children with the syndrome but very different from the normal appearance of these proteins. 

Gozes says, “[The] significance of these findings is that the mutation that causes ADNP syndrome damages a wide range of essential proteins, some of which bind to the tau protein, among other things, and impair its function as well. This creates various pathological effects in the brains and other tissues of children with ADNP syndrome, one of which is the formation of tau deposits, known to be a characteristic of Alzheimer’s disease.” 

She adds that the findings offer hope that “we will ultimately reach the goal of developing a drug or drugs that will help children with autism resulting from genetic mutations.” 

In the earlier research by Chao Tai and colleagues, the researchers found that reducing levels of tau prevented seizures and symptoms of autism in a mouse model of Dravet syndrome—a severe form of epilepsy—as well as reducing symptoms in a second mouse model of autism involving a different genetic mutation.

Citations

“Tauopathy in the young autistic brain: novel biomarker and therapeutic target,” Iris Grigg, Yanina Ivashko-Pachima, Tom Aharon Hait, Vlasta Korenková, Olga Touloumi, Roza Lagoudaki, Anke Van Dijck, Zlatko Marusic, Mirna Anicic, Jurica Vukovic, R. Frank Kooy, Nikolaos Grigoriadis, and Illana Gozes, Translational Psychiatry, July 2020 (free online). Address: Illana Gozes, Elton Laboratory for Neuroendocrinology, Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv, Israel, [email protected]. 

—and— 

“Experimental drug for Alzheimer’s may help children with autism,” news release, Tel Aviv University, July 28, 2020. 

—see also— 

“Tau reduction prevents key features of autism in mouse models,” C. Tai, C. W. Chang, G. Q. Yu, I. Lopez, X. Yu, X. Wang, W. Guo, and L. Mucke, Neuron, February 18, 2020 (epub prior to print publication). Address: [email protected].