Comprehensive coverage

Researchers at Tel Aviv University: many genetic mutations that characterize autism and intellectual disability also appear in the brains of Alzheimer's patients

The researchers found that treatment with an experimental drug called NAP may prevent the negative effect of the mutations on the brain * The article was recently published in the journal Molecular Psychiatry.

Alzheimer's. Illustration: Image by Gerd Altmann from Pixabay
Alzheimer's. Illustration: Image by Gerd Altmann from Pixabay

Researchers at Tel Aviv University, led by Prof. Ilana Gozes from the School of Medicine and the Sagol School of Neuroscience, found a high overlap between hundreds of mutations that characterize children with autism and intellectual developmental disabilities, and mutations in the brains of Alzheimer's patients. The researchers focused especially on mutations in the ADNP gene, which has an important role in brain development and in protecting the structure of nerve cells in the brain. They found that treatment using a shortened segment of the ADNP protein, called NAP, may protect the brain from the effect of the mutations, and help Alzheimer's patients and autistics.

The doctoral students Yanina Ivashko Fahima, Edva Hadar (first notebooks), Iris Grieg, Oksana Kapitansky and Gideon Karmon from the laboratory of Prof. Guzes, Prof. David Gurvitz from the School of Medicine at Tel Aviv University (co-supervisor of Edva Hadar), Michael Gershovitz from the Weizmann Institute of Science participated in the study , and laboratories in the Czech Republic, Spain, Belgium and England. The article was recently published in the journal Molecular Psychiatry.

Prof. Ilana Gouzes: "With the development of DNA sequencing technology, many mutations have been found in hundreds of genes in children with autism and developmental intellectual disabilities in recent years. These are random mutations that were not inherited from the parents, but occurred in the stem cells of the embryo, during cell division. In children, a single mutation in an important gene can cause autism and mental retardation. In the first phase of the research, we wanted to check if mutations also appear in the cells in the brains of Alzheimer's patients, and if there is an overlap between the mutations that characterize Alzheimer's and autism."
The researchers examined samples taken from the olfactory bulb region of the brains of Alzheimer's patients, after their death. RNA sequencing of the genome in the olfactory bulb samples revealed hundreds of mutations. In addition, the researchers checked data from several internet databases, and found mutations in thousands of genes in the brains of Alzheimer's patients - much more (on average per subject) than in a healthy brain. Now they compared their findings to findings from studies of autism-related mutations. "We found a significant overlap: about 40% of the disease-causing gene mutations that we identified in the olfactory bulb of Alzheimer's patients were also found in children with autism and intellectual disability," says Prof. Gouzes.

Prof. Ilana Gozes. Photo: Tel Aviv University spokesperson
Prof. Ilana Gozes. Photo: Tel Aviv University spokesperson

Now the researchers have moved on to an in-depth examination of a specific gene - the ADNP gene, which is responsible, among other things, for the ADNP syndrome which causes autism and intellectual disability, and is known to be also related to Alzheimer's disease. "The ADNP protein, produced by the ADNP gene, was discovered in my laboratory about 20 years ago, and since then we have conducted many studies on it," says Prof. Gouzes. "Over the years, it became clear that ADNP plays a central role in the development of the brain in the fetus, and that its action is related to the Tau protein, which binds to the skeleton of nerve cells in the brain and stabilizes the cell structure, and is known to be damaged in Alzheimer's patients. In the past, we extracted from the ADNP protein a shortened segment called NAP, which serves as a basis for an experimental drug for autism. In the present study we found several new mutations in the ADNP gene in the brains of Alzheimer's patients. We also discovered that as the number of ADNP mutations increases in the patients' brains, the pathology of the Tau protein also increases."

In the next step, the researchers used genetic engineering to inject ADNP with 2 mutations that shorten the protein, as well as Tau labeled with a fluorescent dye, into model cells of brain neurons. The Tau staining test in the living cells revealed that the mutation in ADNP caused damage to the binding of the Tau to the neuron cell skeleton, resulting in a weakening of the cell skeleton. However, it was found that treatment with the experimental drug NAP (also known as 201CP) protected the structure of the nerve cell skeleton from the harmful effect, and the skeleton remained stable and normal. Prof. Guzes points out that these findings indicate that a proper mechanism of action of ADNP is required for the proper attachment of Tau to the cell skeleton, while mutations in ADNP disrupt the mechanism. The return of the NAP segment accelerates the binding of the Tau protein to the cytoskeleton, thus protecting the cell from the harmful effect of mutations in ADNP.

"Our research opens up a new horizon for the research and treatment of Alzheimer's disease and autism," concludes Prof. Gozes. "Until now, Alzheimer's researchers have mainly focused on the amyloid deposits that form in the brains of Alzheimer's patients. Our research directs attention in another direction - mutations that affect the Tau protein, thus causing damage to the structure of the nerve cells in the brain. Moreover, the experimental drug we are developing may help Alzheimer's patients as well as autistics with mutations similar to those of Alzheimer's disease."

It is important to note: the Israeli company Koronis Neuroscience holds the license to develop the drug 201CP, based on the NAP segment, from the Ramot company near Tel Aviv University. The company is developing an experimental drug for ADNP syndrome autism, which is caused by a random mutation in the ADNP gene. The development was done under the designation of an orphan drug by the US Food and Drug Administration (FDA).

for the scientific article

More of the topic in Hayadan:

4 תגובות

  1. Does this mean that people on the spectrum have a particularly high risk of developing Alzheimer's in their old age?

  2. Is there an option in Israel to do a full genetic examination of the fetus and check for the presence of those genes before birth (and to have an abortion if necessary like they do in cases of Down because I really don't want an autistic child).

  3. By chance, they got the same gene that the lab has been researching for 20 years.

    To those who have a hammer in their hand, everything looks like a nail

  4. Is there a statement here that autism is the same as intellectual disability?
    I am interested both from a definitional and scientific point of view in light of the fact that you mentioned that the same gene, ADNP, is responsible for both?
    In other words, is my autistic child retarded?

Leave a Reply

Email will not be published. Required fields are marked *

This site uses Akismat to prevent spam messages. Click here to learn how your response data is processed.