Rare Mutation Found to Prevent Dementia: Shaking up Conventional Wisdom and Offering New Opportunities for Therapy

Shaking up the conventional wisdom about the cause and treatment of dementia
Could be an opportunity to develop new therapies

Scientists have found new clues to pinpoint the cause and treatment of the onset and worsening of Alzheimer’s disease. While studying 1,200 cases of family genetic early-onset patients, he found only one exceptional case, and through his rare mutant gene, he saw the hope of overcoming the limitations of dementia research so far.

A research team at Antioquia University in Colombia published a research paper on this in the international journal Nature Medicine on the 15th. The research team The researchers analyzed the genes and medical history of approximately 1,200 Colombians between the ages of 45 and 50 who had the “paisa mutation,” which causes early-onset dementia. Surprisingly, even with this gene mutation, they found one person who maintained a normal state with only mild cognitive impairment until the age of 67. his brain scan Concentrations of amyloid and tau protein, which are known to cause dementia, were similar to those of other patients with severe dementia. On the other hand, it was confirmed that the concentration of tau protein in the part of the olfactory cortex of the brain, which is related to memory and search ability, remained at a low level.

In particular, the research team analyzed his genes and found that there was a mutation in the lilin protein, which is known to be associated with brain disorders including schizophrenia and autism. So far, little has been known about the role of the rilin protein in dementia. As a result, when the same mutation was created and tested on rats, an even more surprising fact was confirmed. It was observed that the mutated rillin protein chemically modifies the tau protein to prevent it from sticking to brain cells.

As a result of detailed observations, the mutated lilin protein binds to the same receptor as the APOE protein involved in causing Alzheimer’s dementia in people without the Paisa mutation. Previously, the research team had analyzed the genes of women with the Paisa mutation, who developed dementia 30 years later than the average in 2019, and announced the results of a study that found that there was a mutation in the APOE protein. It was also confirmed that a very large amount of amyloid protein was deposited in the brain cells of this woman’s brain.

These findings challenge the conventional wisdom about the cause of Alzheimer’s disease. This is because recently, Alzheimer’s dementia researchers believe that the disease is mainly caused by amyloid protein killing brain cells, and is targeting it as a treatment target. However, even if the amyloid-targeting dementia treatments have been approved by the US Food and Drug Administration (FDA), they show only the effect of mitigating the rate of cognitive decline to a certain extent.

“The fact that this patient was able to maintain mental health for so long despite deposits of amyloid protein in the brain cells suggests that the cause of Alzheimer’s may actually be more complex,” said Yadong Huangmi, a neurology researcher at the Gladstone Institute in San Francisco. “There are many causes of Alzheimer’s disease, and amyloid protein is only one of them,” he explained.

The results of this study are expected to help discover new dementia treatments. This is because, when combined with previous studies, it is hypothesized that strengthening the lilin protein or weakening the APOE protein can protect the brain from dementia. The research team explained, “In the case of Lilin or APOE protein-targeting therapy, it may be more effective in sporadic Alzheimer’s patients with slower progress and mild symptoms than the large family genetic early-onset case found in Colombia.”