2024-05-06 18:28:55
People who carry two copies of the APOE4 gene are almost guaranteed to develop Alzheimer’s disease and develop symptoms at an earlier age. Researchers reported this Monday in a study that could redefine these carriers as carriers of a new genetic form of the mental-debilitating disease.
The reclassification could change the approach to Alzheimer’s research, diagnosis and treatment, according to researchers, whose study was published in the journal Nature Medicine.
“What we’re saying through these data is that this could be a genetic form of this disease and not just a reflection of a risk factor,” said study co-author Sterling Johnson of the Center for Disease Research Alzheimer’s University of Wisconsin with reporters in brief.
Scientists have known for three decades that people with two copies of the APOE4 gene variant have a much higher risk of developing the disease than people with the most common version of the APOE gene, known as APOE3. About 2 to 3% of the general population or 15% of people with Alzheimer’s have two copies of the APOE4 variant.
“This study provides strong data suggesting that people with two copies of this gene are almost guaranteed to develop Alzheimer’s if they live long enough, and will develop Alzheimer’s earlier than people without this gene,” said Alzheimer’s researcher Professor Tara Spiers-Jones. at the University of Edinburgh who were not involved in the study.
Dr. Juan Fortea of the University of Barcelona and his colleagues examined more than 3,000 brains donated by the US National Alzheimer’s Coordinating Center, as well as biological and clinical data from more than 10,000 people from three countries.
They found that 95% of people with two copies of APOE4 – known as homozygotes – had abnormal levels of a protein linked to beta-amyloid called Alzheimer’s in their spinal fluid and 75% had positive brain scans with for amyloid.
Almost all APOE4 homozygotes in the study had higher amyloid levels by age 65 than people who did not carry the risk variant.
The results indicate that APOE4 homozygotes meet the three main criteria for genetic disease: almost everyone with these two variants has Alzheimer’s biology, they develop symptoms at approximately the same rate, and the clinical and biological changes occur in predictable order of, according to. for the researchers.
Professor David Curtis of UCL’s Institute of Genetics, who was not involved in the research, was not convinced. “I can find nothing in this study that would justify the claim that carrying two copies of APOE4 represents a ‘special genetic form’ of Alzheimer’s disease,” he said in a statement.
“No matter how many copies of APOE4 you carry, the underlying disease processes appear to be similar in all Alzheimer’s cases,” he said.
EFFECTS OF TREATMENT
The results could have implications for the Alzheimer’s treatment Leqembi, which was recently approved by Eisai and Biogen, a drug that removes amyloid from the brain.
In clinical trials, patients with two copies of the APOE4 variant had significantly higher rates of cerebral hemorrhage and treatment-related swelling. For this reason, some centers do not treat these patients, said Dr. Reisa Sperling, an Alzheimer’s researcher at Mass General Brigham who worked on the study, in a briefing session with reporters.
The findings suggest that these patients should be treated at a younger age because “we know that they are very likely to become debilitated quickly,” she said.
Dr. Samuel Gandy, an Alzheimer’s researcher at Mount Sinai in New York, said the results show the need to include APOE4 homozygotes in studies designed to prevent the disease before it becomes symptomatic. Sperling is conducting such a study.
Heather Snyder of the Alzheimer’s Association said the findings, if correct, could have significant implications for how disease risk is assessed, how it is studied in clinical trials and how treatments are developed.
The new name would relate to Alzheimer’s disease which develops later in life. Other genetic forms include autosomal dominant Alzheimer’s disease, which is caused by mutations in three different genes, and Down syndrome.
One of the main limitations of the study is that it mainly involved people of European origin. The team said further studies are needed in people of African descent, a population in which APOE4 appears to confer a lower risk of Alzheimer’s disease. (Reporting by Julie Steenhuysen, Editing by Bill Berkrot)
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