Researchers have discovered that a man with a gene mutation that causes early-onset Alzheimer’s disease was protected from developing the disease until the age of 67 due to another mutation in a different gene that blocked the disease from affecting his entorhinal cortex, a brain region associated with memory and cognition. This finding could pave the way for new treatments that delay the onset of Alzheimer’s and transform the approach to therapeutics for the disease. The New York Times reports:
“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-Velasquez is a co-founder of a biotechnology company looking to produce drugs that could act on this research. A drug that delays the disease by two decades is not out of the question, said Dr. Diego Sepulveda-Falla, a neuropathologist at the University of Hamburg in Germany and a member of the research team. The mutation results in a potent version of a protein, Reelin, in the entorhinal cortex. That super-potent Reelin ultimately prevents tangled strands of tau proteins from sticking together and forming the structures that are a characteristic of Alzheimer’s. The idea is to “go in with a syringe and treat only one area” of the brain, he said.
The man with what the researchers are calling “resilience” to Alzheimer’s was part of a decades-long study of 6,000 people living in Colombia who have a gene mutation that causes Alzheimer’s in middle age. Many have agreed to genetic testing, brain scans and, after they die, brain autopsies. A few years ago, the same research group in the current study identified a woman who also was protected from Alzheimer’s. But in her case, resilience was caused by a mutation in a different gene, APOE. Instead of lacking clumps of tau in one small region of her brain, they were missing in her entire brain. But, the researchers say, they think the two patients are revealing a new pathway to treat Alzheimer’s. The two genes that are mutated interrupt a molecular cascade of events needed for tau to aggregate in the brain.
The findings were published in the journal Nature Medicine.