Researchers at Tel Aviv University have developed a new approach to treating Alzheimer's, which has been proven effective in laboratory animals

The researchers focused on the gene known as ApoE, whose defective form (ApoE4) appears in approximately 60% of Alzheimer's patients - and found a way to correct the defect.
The encouraging findings: Laboratory mice treated with the new method recovered from Alzheimer's disease * The study was published in September 2016 in the Journal of Alzheimer Disease

Researchers at Tel Aviv University have developed an innovative treatment approach for Alzheimer's disease.

The researchers chose to focus on the gene known as ApoE, whose defective form (ApoE4) appears in approximately 60% of Alzheimer's patients - and found a way to correct the defect. The encouraging findings: laboratory mice treated with the new method recovered from Alzheimer's disease.

The study, published in September 2016 in the Journal of Alzheimer's Disease, was conducted by Prof. Danny Michaelson, head of the Miriam Levbach Chair for the Study of Molecular Processes in Neurodegeneration at Tel Aviv University, in collaboration with PhD student Anat Bem-Kagan and the Artery company from the USA.

The good garden and the bad garden

"For 20 years, scientists all over the world have been trying to find an effective treatment for Alzheimer's disease, which is the leading cause of dementia in the elderly population - but without success," says Prof. Michaelson. "In the decade between 2002 and 2012, 413 clinical trials were conducted worldwide, testing 244 different substances - and all of them failed. For us, as Alzheimer's researchers, it was clear that it was time to expand the canvas, and offer new directions."

In recent years, it is becoming clear that Alzheimer's is not a single disease, but a broad group of sub-diseases, which ultimately cause the degeneration of nerve cells in the brain. Against the background of this understanding, the researchers from Tel Aviv University concluded, contrary to the concept that was dominant in the past, that apparently there is no magic solution - in the form of a single drug that will help all patients. They decided to focus on a subpopulation of patients with a common denominator - a genetic risk factor, the presence of which increases a person's chances of getting Alzheimer's. The factor chosen was the ApoE gene, which appears in the human genome in two main forms: the good gene ApoE3, and the bad gene ApoE4.

"Already 20 years ago, scientists discovered that about 60% of Alzheimer's patients carry the bad gene ApoE4, and their disease starts 20-10 years earlier - compared to patients who express the gene in its good form," explains Prof. Michaelson. "Despite this, to this day the activity of the kindergarten has not been studied in depth, largely due to the lack of appropriate work methods.
"In recent years, models of laboratory mice with ApoE4 have been developed, and these indeed showed pathological features similar to those of Alzheimer's patients: impaired memory and learning, a smaller number of connections between nerve cells in the brain, and additional damage to the brain tissue, similar to those observed in the brains of patients."

But what is the difference between the good garden and the bad garden? The researchers in Prof. Michaelson's laboratory discovered that the protein produced by the ApoE4 gene binds to a lesser amount of fats, compared to the protein produced by the normal version of the gene, ApoE3. "We still didn't know if this difference has any meaning when it comes to Alzheimer's, but we were looking for a way to increase the amount of lipids that bind to the damaged protein, in order to make it more similar to the normal protein," explains Prof. Michaelson. "We decided to focus on the 'glue' that sticks the fat molecules to the protein molecules - a system called 1ABCA - and try to increase its effectiveness."

At this point, the researchers from Tel Aviv University contacted the company Artery from the USA, which discovered a substance (peptide) that increases and improves the activity of the 'glue' ABCA1. "We injected the substance into mice with the bad gene, simulating Alzheimer's patients, and saw that it indeed penetrates the brain," says Prof. Michaelson. In a short time, the researchers noticed that the treatment worked: the new substance corrected the cognitive and pathological problems in the brains of the model mice, and actually cured them of Alzheimer's.

Prof. Michaelson concludes: "Following the impressive results, we believe that our research opens new directions towards the development of an effective treatment for Alzheimer's. We are convinced that it is very important to expand and deepen the research about the ApoE 4 gene, which plays a central role in the serious disease, and is a clear target for drug development."