The man must have had Alzheimer’s disease in his early 40s – he had a guaranteed gene mutation, or so it seemed. A study of his brain revealed severe wasting and the hallmarks of the disease: rough, hard, amyloid plaques and spaghetti-like tau proteins. But the fatal brain disease did not appear until the man was 67 years old.
Now, through extensive research, it has been possible to find out the reason. Another mutation in another gene prevented the disease from entering, so the person was protected. That small part of the brain is home to neurons involved in memory, objects, navigation, and time perception. And there scientists believe that Alzheimer’s disease began.
A Paper The findings were published Monday in the journal Nature Medicine.
Why it matters: A potential pathway to treatment.
More than six million People in the United States have Alzheimer’s disease, it was very difficult to treat. Yet here is a person with a mutation that causes Alzheimer’s disease, which is very severe and rapid. And the disease has been delayed for two decades. If a drug can do what the mutation does, causing more people to develop Alzheimer’s later in life, the outcome could change.
“This really holds the secret to the next generation of therapeutics,” said Dr. Joseph F. Arboleda-Velasquez, a cell biologist at Massachusetts Eye and Ear in Boston and a member of the research team. Dr. Arboleda-Rodriguez is the co-founder of a biotechnology company that wants to develop drugs that can work on this research.
Dr. Diego Sepulveda-Fala, a neuropathologist at the University of Hamburg in Germany and a member of the research team, is not out of the question of a drug that can delay the disease for two decades. The mutation causes a strong version of the protein reelin in the entorhinal cortex. That supercapacitor ultimately prevents tangled tau proteins from clumping together and forming the structures that are characteristic of Alzheimer’s.
The idea is to “go in with an injection and treat just one area,” he said.
But Dr. Thomas Byrd, a professor of neurology and clinical genetics at the University of Washington, warned that such a treatment is far off in the future and may be impossible. Dr. Bird was not involved in the study.
The entorhinal cortex is a very small area. “We don’t know what kind of damage it will cause, sticking needles and throwing them in chemicals.”
Background: Newly adapted from ongoing research.
What the researchers call Alzheimer’s resistance was part of a decade-long study of 6,000 people in Colombia who had a gene mutation that causes Alzheimer’s disease in middle age. Many agreed to genetic testing, brain scans, and, after death, brain autopsies.
A few years ago, the same research team in the current study found that a woman was protected from Alzheimer’s. But in her case, the resistance was caused by a mutation in a different gene, APOE. Instead of missing clumps of tau in a small part of her brain, they disappeared in her brain.
But the researchers think that the two patients are revealing a new way to treat Alzheimer’s. The two mutated genes interrupt the molecular events required for tau to be synthesized in the brain.
What’s next: More research and integrative therapies.
The hypothesis that a drug might protect the entorhinal cortices of other patients needs further research. But animal studies are already underway, Dr. Arboleda-Velasquez. The team injected a mutant form of reelin into the brain region of mice with Alzheimer’s-like disease to see if it was protective.
A member of the research team, Dr. Eric Reimann, executive director of the Banner Alzheimer’s Institute in Phoenix and a consultant to several pharmaceutical companies, said the future may include new therapies. The hope is to prevent the build-up of amyloid and tau and delay Alzheimer’s in people who have been exposed for a long time, and this is not a problem.