Scientists suggest there is a new form of genetic Alzheimer’s

In a study that has gone around the world and was published in the Natrue Medicine, A team of researchers claims to have found a new form of genetic Alzheimer’s. In short, they found that more than 95% of people over 65 who have two copies of the APOE4 gene—that is, APOE4 homozygotes—show biological features of Alzheimer’s in the brain. Or, in other words, they present biomarkers associated with this disease.

The study, led by Juan Forteadirector of the Memory Unit of the Neurology Service of the Sant Pau Research Institute, in Spain, also reveals that these patients develop the pathology earlier than those with other variants of the APOE gene.

“This represents a reconceptualization of the disease or what it means to be homozygous for the APOE4 gene. This gene, known for more than 30 years, was known to be associated with an increased risk of developing Alzheimer’s. We now know that virtually all people who have this duplicated gene develop it. It is important because they are between 2 and 3% of the population,” he details.

“In addition, this variant accounts for 15% of all Alzheimer’s cases. Normally, we say that the causes of this disease are not known, but with this study we can say that we can explain those 15% of cases,” Fortea told the Spanish newspaper El País.

In this work, the researchers evaluated clinical, pathological and biomarker changes in APOE4 homozygotes to determine their risk of developing Alzheimer’s.

To do this, they used data from 3,297 brain donors, including samples from 273 APOE4 homozygotes from the National Alzheimer’s Coordinating Center (US) and clinical and biomarker data from more than 10,000 people, including 519 APOE4 homozygotes from five large European and US multicenter cohorts of subjects with disease biomarkers.

The results suggest that virtually all APOE4 homozygotes showed the pathology and had higher levels of biomarkers associated with the disease at age 55, compared to people with the APOE3 gene.

At age 65, more than 95% of APOE4 homozygotes showed biomarkers such as abnormal levels of amyloid in the cerebrospinal fluid—a hallmark of Alzheimer’s—and 75% had positive amyloid scans.

An uncomfortable question

The authors suggest that the genetic variant of the APOE4 gene is not only a risk factor for Alzheimer’s, as previously thought, but it could also represent a different genetic form of the pathology.

For these experts, the findings could be useful for the development of individualized prevention strategies, clinical trials and treatment approaches aimed at this specific population.

“The data clearly show that having two copies of the APOE4 gene not only increases the risk, but also anticipates the onset of Alzheimer’s, which reinforces the need for specific preventive strategies,” he says. Alberto Lleóresearcher at the Neurobiology of Dementia Group in Sant.

Victor Montalwho actively participated in this study during his stay in Sant Pau and now analyzes the molecular structure of the APOE gene at the Barcelona Supercomputing Center, concludes that “the results emphasize the importance of monitoring APOE4 homozygotes from an early age for preventive interventions.” .

But this study also raises an uncomfortable question: Would someone be willing to know, through a genetic test, if they have double APOE4 and thus know if they are going to develop Alzheimer’s? “It all depends on how you manage the anxiety of knowing that you have, for example, an 80% chance of suffering from Alzheimer’s,” Fortea responded to El País. “The other day he was talking to a colleague who said that he would never do it; I believe that he will do it.”