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Dr Christophe de Jaeger (Longevity and geriatrics)
While he was genetically condemned to develop early Alzheimer’s, a Colombian defied all predictions by presenting only mild dementia at the age of 70. A medical case that brings a new key to the fight against the disease.
Alzheimer’s is a cognitive degeneration that concerns about one million French people, but which remains mysterious and has no treatment. New data studied all over the globe, however, allow us to know a little more every day about the mechanism at the origin of the disease. Today is the medical case of a man genetically predestined to develop early Alzheimer’s which is of interest to medicine: against all expectations, he was spared dementia until an advanced age thanks, it seems, to it, to a genetic change.
A protein would have protected humans against disease
According to the study published in Nature Medicine on May 15, the man in question was part of a large Colombian family, many of whose members inherited a mutated gene called presenilin-1, or PSEN1. However, carriers of PSEN1 are almost certain to develop Alzheimer’s disease at a relatively young age, between 40 and 50 years old. However, nothing to report on the side of our subject, who will develop memory and thinking problems only at 72 years old, before experiencing a decline and an infection. The man died of pneumonia aged 74, but by all indications he should have had memory and thinking problems…two to three decades earlier.
Even more surprisingly, during the autopsy, the doctors discovered that his brain was nevertheless loaded with beta-amyloid and tau, two proteins that accumulate in the brains of people with Alzheimer’s disease.
But according to a genetic analysis, the man had benefited from a rare change in a gene via a protein called reelin, which helps nerve cells communicate. The enhanced reelin protein here appeared to protect a very specific part of the human brain, an area behind the nose at the base of the brain called the entorhina cortex.
Two cases for a new line of study
This is the second time the team studying this extended family has found someone who has defied their “genetic destiny”. In 2019, scientists reported the case of a woman who should have developed early Alzheimer’s disease but retained her memory and thinking skills until she was 70. In her case, the patient carried two copies of a change in her APOE3 gene which has been dubbed the Christchurch mutation. Like reelin, APOE is a signaling molecule known to play a role in increasing a person’s risk of Alzheimer’s.
The researchers thus discovered a link between these two cases: the cell receptors for reelin are the same receptors as for APOE. “These two patients point a direction. They tell us: Hey, this is the way. This is the way forward for extreme protection against Alzheimer’s disease.” said Arboleda-Velasquez, lead author of a new human study.
A work which requires vast studies, and which is only at its beginnings. The Harvard team announces, however, that it is already working to develop a therapy based on these discoveries.
“An open path to multiple research”
For Dr. Chistophe De Jaeger, a physiologist specializing in human aging, this is an event that can be described as explosive in research against Alzheimer’s.
“There are rare families who genetically encounter symptoms of cognitive disorders from the age of 40. The subject, coming from one of these families, experienced moderate dementia at age 72, 30 later than expected. It’s already huge! But what is even more surprising is that at his autopsy, the researchers found signs of dementia well established in the brain. This means that the reeline protein mentioned did have a protective effect on the subject. Inevitably, it can excite many researchers!”.
An exciting announcement in the medical field, certainly, but which does not make it possible to consider a treatment quickly.
“Researchers say it themselves, we are not saying that everyone should be given reeline. On the other hand, it is a possible protective mechanism, which is new, and one can imagine that if this protein is capable of stemming the disease, of delaying it by 30 years (without curing it however), if we can push back the illness at the age of 95 of a person, this is very interesting. It is therefore a track that offers multiple research possibilities” concludes our expert.