More than 30 years ago, researchers identified variants of the Apoe gene as risk factors for Alzheimer’s. Now, a Spanish team suggests that carriers of two copies of the Apoe4 version are, in fact, patients with a different type of neurodegenerative disease, of genetic origin. The discovery, published in the journal Nature Medicinehas implications for diagnoses and searches for treatments for the disease, they stated in an online press conference.
According to Juan Fortea, director of research in neurology and mental health at the Sant Pau Research Institute, in Barcelona, between 2% and 3% of the world’s population carries two copies of Apoe4 in their DNA. Fortea, leader of the study, explains that, although the clinical manifestations are similar, Alzheimer’s is not a single disease. A version that has been studied for more than a decade, for example, is the early-onset version, known as Daip. In this case, symptoms appear before the age of 65 and there is a strong genetic and hereditary relationship.
For the team, the results of the study indicate that Apoe4 homozygotes — double copy of the gene — may represent a genetically determined group of the disease. “We propose a reconceptualization of Alzheimer’s. Until now, Apoe variants are considered risk factors. But our suggestion is that the case of homozygotes be included in the growing family of genetically determined Alzheimer’s disease”, he argues.
Test
One of the implications of the finding is that testing for Apoe4 duplicity should be considered when middle-aged people emerge with symptoms of dementia, believes Paul Matthews, leader of the UK Dementia Research Institute at Imperial College London. “People with Apoe4 homozygotes generally develop symptoms around the same time, have a similar rate of progression, and have easy-to-identify biomarkers as the disease progresses, says Matthews, who was not involved in the study. “So it’s an attractive population to target. clinical trials of new treatments for the disease.”
The Catalan group’s discovery is based on data from 3,297 brains donated to science for the National Alzheimer’s Center in the United States. Of these samples, 273 were from patients with double Apoe4. The researchers also evaluated clinical exams and biomarkers of more than 10,000 people with dementia — including 519 gene homozygotes — from five large European studies.
The results confirm that practically all people with the double variant had Alzheimer’s and had more markers of the disease in their bodies at age 55, compared to individuals with the Apoe3 version of the gene. At 65, 95% with homozygous Apoe4 had abnormal levels of beta-amyloid protein in the brain, a known early pathology of the disease.
Benefit
“The data clearly shows that having two copies of the Apoe4 gene not only increases the risk, but also anticipates the onset of Alzheimer’s disease, reinforcing the need for preventive actions and specific strategies”, points out Victor Montal, co-author of the study and specialist in image analysis of neurodegenerative diseases. “It is clear that this is a genetic form of the disease.”
Reisa Sperling, director of the Alzheimer’s Research and Treatment Center at Brigham and Women’s Hospital in the United States, and co-author of the study, believes that the discovery could benefit those with the double copy of the variant, before clinical symptoms, such as forgetfulness, occur. manifest themselves. As these patients have a greater accumulation of amyloid protein in the brain, when identified through a genetic test, they would have the chance to receive treatment earlier. “That, to me, is the most important aspect of our study.”
Currently, there are two drugs approved for mild Alzheimer’s on the international market, which work by delaying the symptoms of the disease. However, in the United States alone, which leads in terms of research on the disease, there are currently at least 500 clinical trials, according to the country’s National Institute on Aging.
Word from an expert // Otávio Castello, geriatrician, professor of psychiatry and medical psychology at the University of Brasília (UnB)
Genetic counseling
The study brings a paradigm shift in relation to the Apoe4 allele. Each of us has two alleles — one we got from our father, one we got from our mother. What we already knew was that one Apoe4 slightly increases the risk of Alzheimer’s disease, and two increases it even more. But we weren’t talking about cause. What this study indicates is that what we have been treating as a risk factor may be a determining factor in having the disease. It is important to remember that genetics are not modifiable. However, it accounts for less than 10% of the risk factors for developing the disease, so the person can control the others, such as treating hypertension, diabetes, depression, pushing the onset of Alzheimer’s further. If a person decides to take a test to find out if they have a genetic risk for the disease, it is a process that needs to be conducted by a specialist doctor, as there is still no treatment or cure for Alzheimer’s. The person needs to be prepared to deal with information. Remembering that this testing is not available in laboratories, the health plan does not cover it and the majority is carried out abroad. It is a process that must be conducted by a specialist in the field. Not the geriatrician, the psychiatrist or the neurologist, but the medical geneticist.
Genetic counseling
The study brings a paradigm shift in relation to the Apoe4 allele. Each of us has two alleles — one we got from our father, one we got from our mother. What we already knew was that one Apoe4 slightly increases the risk of having Alzheimer’s disease, and two increases it even more. But we weren’t talking about cause. What this study indicates is that what we have been treating as a risk factor may be a determining factor in having the disease. It is important to remember that genetics are not modifiable. However, it accounts for less than 10% of the risk factors for developing the disease, so the person can control the others, such as treating hypertension, diabetes, depression, pushing the onset of Alzheimer’s further. If a person decides to take a test to find out if they have a genetic risk for the disease, it is a process that needs to be conducted by a specialist doctor, as there is still no treatment or cure for Alzheimer’s. The person needs to be prepared to deal with information. Remembering that this testing is not available in laboratories, the health plan does not cover it and the majority is carried out abroad. It is a process that must be conducted by a specialist in the field. Not the geriatrician, the psychiatrist or the neurologist, but the medical geneticist.
Otávio Castello, geriatrician, professor of psychiatry and medical psychology at the University of Brasília (UnB)
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