By Yosef Scher, Science and Technology Senior Editor
Earlier this summer, Diego Sepulveda-Falla and his team found an unexpected discovery that may help physicians treat people with Alzheimer’s disease in the near future: a rare genetic mutation that protects people from developing Alzheimer’s disease for decades. The study published in Nature Medicine is exciting news for humanity, considering that the condition is one of the leading causes of death worldwide. In fact, Alzheimer’s disease currently “affects 6.7 million Americans age 65 and older,” and “1 in 9 people age 65 and older (10.7%) has Alzheimer’s.” More importantly, though, it has been proven that the older you get, the higher your risk of developing the debilitating disease. As the average lifespan for people continues to rise, the number of people who develop Alzheimer’s will grow unless scientists devise a way to slow down the progression or find a cure for the debilitating disease.
While many people know the general symptoms of Alzheimer’s disease, such as memory loss and trouble speaking, few know there are two primary forms of Alzheimer’s: early-onset Alzheimer’s disease and late-onset Alzheimer’s disease. Most people who develop the disease have late-onset Alzheimer’s disease. Symptoms begin to manifest in a person’s mid-60s. While researchers have not discovered a specific gene that causes late-onset Alzheimer’s disease, the consensus is that having a particular allele, or variant, of the Apolipoprotein E (APOE) gene on Chromosome 19, increases a person’s risk, but does not guarantee, that the person with the mutation will develop Alzheimer’s. In contrast to late-onset Alzheimer’s disease, early-onset Alzheimer’s disease affects people in their early 30s to mid-60s. Moreover, unlike late-onset Alzheimer’s disease, scientists have found a solid genetic understanding of the causes of this disease; three genes can be mutated that result in early-onset Alzheimer’s disease, unless you have a protective mutation in a specific gene that staves off the disease for decades.
For the second time in four years, scientists found a rare mutation in a specific Colombian family who should be showing signs of early-onset Alzheimer’s disease in their early 30s and 40s, but do not have the disease because of a mutation in the RELN gene. This news is very exciting, as scientists hope this discovery “could lead to new treatments for all forms of Alzheimer’s.” Interestingly, this mutation differed from the mutation found in a Colombian woman in 2019, who had a mutation in the APOE gene known as the Christchurch variant. While both individuals had different mutations in different genes, scientists found many similarities between the two mutations. For example, the Colombian man and woman’s brains had an abundance of amyloid plaque, which are “aggregates of misfolded proteins that form in the spaces between nerve cells.” Even though there were similarities, the researchers also noted stark differences between the two cases. Tau, another misfolded protein, typically seen in Alzheimer’s patients, was much more prevalent in the man’s brain than the woman’s. Researchers believe that the reason that this occurred was because of where the “two protective genes are active in the brain.” Unlike the APOE gene, which is active everywhere in the brain, the RELN gene is only active in a few places of the brain. As such, the woman, who had a protective mutation in the APOE gene, had lower levels of misfolded tau protein buildup compared to the man, who had a mutation in the RELN gene. The good news is that both mutations appear to reduce the formation of tau tangles.
Even though this is a significant breakthrough for the scientific community, scientists are hesitant to make any conclusions from the results because of the small sample size. That being said, scientists believe this discovery can “serve as a useful guide for drug discovery” for all forms of Alzheimer’s disease in the coming months.