[과학을읽다]Discovery of a rare mutation to prevent dementia

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

Scientists have found a new clue to identify the cause and treatment of Alzheimer’s onset and progression. Studying 1,200 cases of familial early-onset genetic 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 the University of Antioquia 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 about 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 condition with only mild cognitive impairment until the age of 67. his brain scan Concentrations of amyloid and tau protein, 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 linked to memory and search ability, remains 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 linked to brain disorders including schizophrenia and autism. Until now, little is 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 startling fact was confirmed. The mutated rillin protein was seen to chemically modify 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 average in 2019, and published the results of a study that found a mutation in the APOE protein. It was also confirmed that a large amount of amyloid protein had been 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 targeting it as a treatment target. However, even if the dementia treatments that target amyloid have been approved by the US Food and Drug Administration (FDA), they only show the effect of mitigating the rate of cognitive decline to some extent.

“The fact that this patient was able to maintain mental health for so long despite deposits of amyloid protein in 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 just 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, the hypothesis is that strengthening the protein lilin or weakening the protein APOE can protect the brain from dementia. The research team explained, “In the case of Lilin or APOE protein targeting therapy, it could be more effective in sporadic Alzheimer’s patients with slower progress and mild symptoms than the large familial genetic early onset case found in Colombia.”