Chinese scientists hope Alzheimer’s gene discovery will pave way for new treatments
- The team identified a previously unknown genetic mutation that causes the disease when studying a mother and two siblings diagnosed with dementia
- Researchers say the discovery could open the door to the development of new drugs and treatments for the condition
Chinese researchers have identified a new gene mutation that can cause Alzheimer’s disease, a discovery the authors say could help develop new drugs to treat the condition.
Alzheimer’s disease is the most common form of dementia and a major public health problem across the world.
About 44 million people around the globe live with Alzheimer’s, according to a 2019 study by the journal Lancet Neurology.
Scientists have previously identified mutations in three genes that result in the increased production and abnormal accumulation of a protein known as amyloid beta, which is characteristic of Alzheimer’s.
However, these genetic defects occur in only about 10 to 20 per cent of familial cases, meaning that more genes and mechanisms that cause the disease remain unknown, according to the researchers from Capital Medical University’s Xuanwu Hospital in Beijing.
Their new study, published in the peer-reviewed journal BMC Medicine on June 26, found a mutation in a different gene – named ZDHHC21 – that can also cause Alzheimer’s.
Jia Jianping, corresponding author of the study and a researcher at Xuanwu Hospital, said the impact of the discovery would be enormous.
“Previous studies reported mutations in the three recognised genes … but our study discovered a totally new gene in which a mutation is responsible for Alzheimer’s disease,” Jia said.
He added that the discovery of the new gene mutation and mechanism may bring a new approach to drug development and bring new hope for the treatment of Alzheimer’s.
Jia said the study was the accumulation of 10 years of research.
Jia and his team established the Chinese Familial Alzheimer’s Disease Network in 2002 to study the genetic features of Chinese people with Alzheimer’s disease.
The network enrolled a total of 1,330 patients with Alzheimer’s or mild cognitive impairment across 404 genetic pedigrees.
They found that 83 per cent of the pedigrees did not carry the three previously known mutations, suggesting that other genes and mechanisms may be involved.
In 2015, a 55-year-old woman went to the hospital’s neurology department because of a gradual and progressive memory decline. She was diagnosed with Alzheimer’s disease, as well as her mother and one brother.
The team performed exome sequencing – a technique used to sequence only the protein-coding regions of the genome – on the woman and her family members and identified a novel mutation in one gene that may have caused the disease.
The exome represents less than two per cent of the human genome but it contains about 85 per cent of the genetic variations that are known to cause diseases.
The mutation was detected in her family members with Alzheimer’s disease but was not found in those who did not have the disease, according to the study.
The researchers then used genome-editing technology to create the mutation in mice and found evidence suggesting that it induced impaired learning ability and decreased memory retention.
The study said the mutation also enhanced a process known as palmitoylation, which changes the way the protein behaves and can affect the function of the brain and nervous system.
In this case it contributed to an increase in the amyloid beta protein, causing Alzheimer’s disease.
“Our results indicate that palmitoylation modification of specific substrates is an alternative driving mechanism of Alzheimer’s disease and suggest that palmitoylation is a promising target for drug therapy,” the study concluded.
