United States: In a study published on Monday, experimenters set up that individualities with two clones of the APOE4 gene are nearly certain to have Alzheimer’s and experience some symptoms before in life. This finding may reclassify carriers of the gene as having a certain heritable variant of the degenerative illness.
The researchers, whose work was published in the journal Nature Medicine, believe that the reclassification may have an impact on Alzheimer’s disquisition, opinion, and treatment strategies.
Link to Alzheimer’s Disease
Researchers Sterling Johnson of the University of Wisconsin’s Alzheimer’s illness Research Center, who co-authored the paper, told reporters at a briefing that “through these data we are saying that perhaps this is a genetic form of this disease, not merely a risk factor indication.”
APOE4 Gene Variant
For thirty years, researchers have been aware that individuals carrying two copies of the APOE4 gene variation are notably more likely to acquire the illness than those carrying the most prevalent APOE gene variant, APOE3. Two copies of the APOE4 variation are found in 2–3% of the general population, or 15% of those with Alzheimer’s disease.
“This study adds compelling data to suggest that people with two copies of this gene are almost guaranteed to develop Alzheimer’s if they live long enough, and that they will develop Alzheimer’s earlier than people without this gene,” said professor Tara Spires-Jones, a University of Edinburgh researcher on Alzheimer’s disease who was not involved in the study.
Research Findings and Clinical Data
Along with molecular and clinical data on over 10,000 people from three countries, Dr. Juan Fortea of the University of Barcelona and associates examined over 3,000 donated brains from the National Alzheimer’s Coordinating Center in the United States.
They discovered that at the age of 65, at least 95% of homozygotes, or those with two copies of the APOE4 gene, had abnormally high amounts of beta amyloid, a protein linked to Alzheimer’s disease, in their spinal fluid, and 75% had amyloid-positive brain scans.
Concerns and Criticisms
Compared to those who did not inherit the risk mutation, nearly all APOE4 homozygotes in the research had greater levels of amyloid at age 65.
According to the researchers, the results imply that APOE4 homozygotes satisfy the three primary requirements for being classified as a genetic illness: almost all individuals carrying these two mutations have the biology of Alzheimer’s disease; they experience symptoms at roughly the same pace; and the clinical and biological alterations follow a predictable pattern.
Not engaged in the research, Professor David Curtis of the UCL Genetics Institute was not persuaded. “I do not see anything in this paper to justify the claim that carrying two copies of APOE4 represents some ‘distinct genetic form’ of Alzheimer’s disease’,” he said in a statement.
Implications for Clinical Trials and Therapies
“No matter how many (copies) of APOE4 one carries the underlying disease processes seem similar across cases of Alzheimer’s disease,” he added.
The results may affect the recently licensed Alzheimer’s therapy Leqembi from Biogen (BIIB.O) and Eisai (4523.T), opens new tab, which is a medication that clears the brain of amyloid.
Patients having two copies of the APOE4 variation in clinical trials experienced significantly greater rates of treatment-related brain hemorrhage and edema. In a conference with reporters, Dr. Reisa Sperling, an Alzheimer’s researcher at Mass General Brigham who worked on the study, stated that some facilities do not treat these patients as a result.
Need for Further Research
According to the findings, “we know they’re very, very likely to progress to impairment quickly,” therefore it’s best to start treating them earlier.
According to Dr. Samuel Gandy, a researcher on Alzheimer’s disease at Mount Sinai in New York, the results emphasize the necessity of enroling homozygotes with APOE4 in studies intended to stop the illness before symptoms appear. Sperling is running one of these experiments.
If the results are accurate, as stated by Heather Snyder of the Alzheimer’s Association, they may have a substantial impact on how disease risk is determined, how it is investigated in clinical trials, and how therapies are created.
Later-life onset Alzheimer’s would be given this new classification. Other genetic variations include Down syndrome and autosomal-dominant Alzheimer’s disease, which is brought on by mutations in three distinct genes.
The study’s main drawback is that the majority of its participants were of European descent. The researchers concluded that further research is necessary in African Americans, a community in which APOE4 appears to be associated with a decreased incidence of Alzheimer’s disease.