Researchers from the Research Institute of the Hospital de Sant Pau in Barcelona have identified a new form genetics of the disease of Alzheimer’s which affects virtually everyone who has two copies of the gene APOE4.
The research, published this Monday in the journal Nature Medicinemodifies the conception of the effects of this gene and opens the door to new approaches in the research of the disease. Alzheimer’sthe most common form of dementia that affects millions of people around the world.
“It’s a pretty profound reconceptualization, because we’re saying that, if you have this type APOE4with more than 95% probability you will develop the biology of the disease Alzheimer’s at 65 years old,” explained the director of the Memory Unit of the Neurology Service of Sant Pau, Juan Fortea.
For decades, the scientific community has known that APOE4 is associated with an increased risk of developing Alzheimer’sbut until now it had not been determined that it could be a determining cause of the disease.
“Many of the genes that are published and investigated are very important from a pathophysiological point of view – as possible factors for the development of the disease – but they do not inform the person or family of the individual risk” of ending up suffering. Alzheimer’sthe specialist has pointed out.
With this new research, the variant genetics of the gene APOE4 It is no longer just a risk factoras was believed until now, but represents a new form genetics of the disease of Alzheimer’s.
In this way, it would be at the same level as two other forms that are already classified as such: Alzheimer’s associated with Down syndrome – they are two extremely genetically connected conditions – and Alzheimer’s autosomal dominant – a rare type of dementiaof genetic component-.
In the case of APOE4it is estimated that between 2 and 3% of the general population has this variant of the gene and, among those who have Alzheimer’srepresents between 15% and 20%.
“We are talking about millions of people in Spain and many more millions in Europe and around the world, so we are facing an opportunity,” Fortea highlighted.
In this sense, the finding may allow, from now on, research, prevention and existing treatments to stop the progression of the disease, plus those that will come soon, be better focused on this segment of the population with this characteristic genetics.
Priority in treatments
“These people have to be among the first on the list when it comes to receiving these – therapeutic – interventions and probably require much more exhaustive follow-up than people who have other less risky genetic conditions,” the researcher judged.
At the same time, in future research, having this definition in a new way Alzheimer’s genetics It can be used to develop clinical trials aimed at this specific group, to advance a model of personalized medicine.
“He Alzheimer’s gives us this opportunity, because it is a slow disease, lasting decades, in which we can already determine the presence of biology of the Alzheimer’s with biomarkers – such as TAU and beta amyloid proteins – so it is about promoting clinical trials that can prevent or delay the development of the disease,” Fortea noted.
Although the researcher sees this “new era of Alzheimer’s“, thanks to the existing tools and those that are being investigated “to modify the course of the disease”, has indicated that it is “premature” to recommend population screening prior to symptoms to determine who has APOE4nor is it done with amyloid levels, largely because there is no specific treatment that cures the disease.
For the research made public this Monday, the researchers evaluated the clinical, pathological and biomarker changes in homozygotes APOE4 -two copies of the same gene- to determine the risk of developing Alzheimer’s.
They used data from 3,297 brain donors, including samples from 273 homozygotes. APOE4 of the National Coordination Center Alzheimer’s of the United States.
Also clinical and biomarker data from more than 10,000 people, including 519 homozygotes APOE4 of five large cohorts from Europe and the United States, including the Pasqual Maragall Foundation.
The results suggest that practically all homozygotes APOE4 showed pathology Alzheimer’s and had higher levels of biomarkers associated with the disease at age 55 compared to people with another type, the APOE3.
At age 65, more than 95% of homozygotes APOE4 showed abnormal levels of amyloid protein in the cerebrospinal fluid – a key early pathological feature in Alzheimer’s – and 75% had positive amyloid scans.
