Scientists have discovered a new genetic variant of Alzheimer’s that highlights the need for specialised treatments and prevention strategies.
Researchers in the US found that almost all people with two copies of APOE4 (also known as APOE4 heterozygotes) are at risk of developing symptoms of this neurological disorder.
This gene has already been linked to a higher risk for Alzheimer’s.
Scientists now believe that 95% of people over 65 who carry two copies APOE4 will show early symptoms of Alzheimer’s disease. This is a genetic form of Alzheimer’s.
They also added that these people develop the condition sooner than those who have other variants of APOE genes.
The findings published in Nature Medicine are based on data collected from over 10,000 patients, and pathological data of more than 3,000 donors.
Dr Juan Fortea is the director of research on neurological diseases, neurology, and mental health in the Sant Pau Research Institute, Barceclona Spain. He said that these data “reconceptualise the disease, or what it means for someone to be homozygous with the APOE4 genes.”
This gene has been well-known for more than 30 years, and was associated with an increased risk of Alzheimer’s.
Now we know that almost all individuals who have this duplicated gene develop Alzheimer’s biology.
He stated that the findings were important, as APOE4 homozygotes make up between 2% to 3% of the population.
According to researchers, this warrants the development specialised research strategies and treatment approaches for these individuals.
Dr Reisasperling, professor of neurology at Harvard Medical School and director of Brigham and Women’s Hospital, Boston and Massachusetts in the US said: “This research suggests that we treat them early, as they are likely to progress quickly to impairment.
We need to consider how we will treat APOE4-carriers.
These individuals are desperate. They have seen the disease in both their parents.
We now know that nearly all individuals who have this gene duplicated develop Alzheimer’s disease biology
Three genes APP, PSEN1 or PSEN2 are known to be responsible for a rare type of Alzheimer’s called ADAD. (early onset autosomal dominance Alzheimer’s).
This disease is inherited.
APOE, one of the many genes linked to Alzheimer’s disease, comes in three variations: APOE2, APOE3, APOE4.
Each person carries two copies of APOE. One copy is inherited from each parent.
Having two copies of the APOE4 gene increases the risk up to 12 times.
The team discovered that people with two copies APOE4 had signs of the disease at age 55 compared to those who have another gene variant such as APOE3.
By the age 65, 95% of the patients had abnormally high levels of amyloid protein in the fluid surrounding the brain and the spinal cord. This is a major sign of Alzheimer’s.
Currently, we don’t recommend that people get genetically tested for APOE unless they are taking part in research. However, this could change in the future.
APOE4 homozygotes over 65 years old had abnormal amyloid protein buildup in their brains. This is seven to ten years earlier than symptoms developing for other APOE variations.
Professor Jonathan Schott of Alzheimer’s Research UK commented on the study. “In this well-conducted large study, researchers found that people with two copies APOE4 in their brains had Alzheimer’s disease by the time they reached mid-60s.
These individuals are more likely to suffer from dementia, and they tend to age earlier than other APOE combinations.
“At present, we do not recommend that people undergo genetic testing for APOE unless they are taking part in research. However, this could change in the future.”
He said Alzheimer’s UK funds research to try and understand why the APOE4 genes increases the risk of developing disease.
Dr Richard Oakley is the associate director for research and innovation at Alzheimer’s Society. He added, “This study shows that this gene could play an important part in Alzheimer’s development. Its presence may not only be a risk factor but also indicate a novel form of Alzheimer’s.”
The study’s findings suggest that, in the future, it may be necessary to consider a person’s genetics as part of a plan to reduce the risk of Alzheimer’s or to treat the disease if already present.