Ongoing research at an Israeli university may lead to vaccines that can teach our immune systems to better fight Alzheimer’s disease.
An Israeli researcher who is working on a vaccine for Alzheimer’s has discovered that it is possible to test and measure specific immune responses in mice carrying human genes and to anticipate the immune response in Alzheimer’s patients.
The research at Ben-Gurion University of the Negev (BGU) could lead one day to specific Alzheimer’s vaccines that reduce plaque, neuronal damage and inflammation associated with the disease.
Today around 5.3 million people in the US alone suffer from Alzheimer’s, a debilitating and progressive disease that destroys the brain cells causing memory loss, according to the Alzheimer’s Association. It is a fatal disease, and is the seventh leading cause of death in the US.
Amyloid beta-peptide accumulates in the brain of Alzheimer’s patients where it appears to promote neuronal damage. In an article, recently published in the Journal of Immunology, BGU researcher Dr. Alon Monsonego determined that introducing A-beta into the brain triggers a natural immune response that can be detected in humans.
Most importantly, the research team showed that the specificity and magnitude of this body response to A-beta depends on certain key genes of the immune system, which are highly polymorphic in the population (this means that except for identical twins, almost each of us has a different combination of genes, termed “HLA alleles”).
Of mice and men
This research took an unusual approach combining humans and humanized mouse models. “We began with characterizing the genes in humans in collaboration with the laboratories of Dr. Weiner and Dr. Selkoe at Harvard, then did the same study in mice using a mouse model of multiple sclerosis with the laboratory of Dr. Altmann – Imperial College School of Medicine, UK,” Monsonego said.
“We then generated a humanized mouse model of Alzheimer’s, with a specific gene that was present in approximately 30 percent of our study group (HLA DR15 allele). Conceivably, those people that have this gene could receive the same vaccine which will teach a person’s immune system to better fight the disease.
“As in other mouse models of the disease, “Monsonego continued. “We show that with aging, A-beta aggregates accumulate in brain areas of cognitive functions and stimulate an inflammatory reaction in the brain.”
However, he adds, stimulating an immune response to A-beta in these humanized mice not only resulted in a highly efficient clearance of A-beta (plaque) from the brain, but also in a markedly reduced inflammatory reaction.” Furthermore, we were able to predict that the characteristics of immune response in mice were the same as in the humans,” said Monsonego.
He believes the study provides the basis for developing an individual-based (personalized medicine) immunotherapeutic approach to Alzheimer’s disease since different populations will respond differently to a vaccine based on their genetic background.
“Now that we’ve proven we can anticipate the specific responses for several abundant genes in the population, further study is needed to ensure safety and efficacy in our humanized mouse model of Alzheimer’s,” said Monsonego.
Monsonego, who holds the Zehava and Chezy Vered Career Development Chair for the Study of Alzheimer’s and Neurodegenerative Diseases, is a member of BGU’s Shraga Segal Department of Microbiology and Immunology and the National Institute for Biotechnology in the Negev.
The research is funded in part by the Israel Science Foundation, the Alzheimer Association and by New York real estate developer Leonard Litwin and the Aaron Gural family.