;Resize=(1200,627)&impolicy=perceptual&quality=mediumHigh&hash=fda0773926139de5831465d67a54764de999c479ba467214336749ffb83c1ba5 "Dementia: Rare gene mutation in patient could protect others from Alzheimer’s")
A patient with a rare gene mutation provides new starting points against dementia. Because this man has a gene variant that saved him from developing Alzheimer’s despite his hereditary predisposition. The effect could help stop the process in other sufferers as well.
So far there is no cure for Alzheimer’s dementia, but new active ingredients such as the antibody preparations donanemab or lecanemab can at best slow down the progressive destruction of brain cells. They attack the plaques of misfolded beta-amyloid proteins, which are considered a key symptom of dementia. However, fibrils made of misfolded tau proteins in the brain cells are also involved in the degradation – they also accelerate mental degradation.
Symptom-free despite Alzheimer’s mutation
A rare gene mutation could now provide a possible therapeutic approach against the tau proteins. This gene variant was discovered in a patient suffering from an early onset, hereditary form of Alzheimer’s dementia – actually. Because although this man carried the disease-causing Paisa mutation in his genome, he didn’t get sick. Instead of developing the first symptoms of dementia in his mid-40s, as is usual for this form of Alzheimer’s, he remained symptom-free until his early 70s.
But why? To find out, an international team led by Francisco Lopera from the University of Antioquia in Colombia examined the genome of the man who died at the age of 74. They not only came across the pathogenic Paisa mutation, but also another, very rare gene mutation. It is only the second case worldwide of a person who was saved from Alzheimer’s by a gene mutation. The researchers published the case in the journal Nature.
Protective mutation in the Reelin gene
“It’s exciting that Mother Nature is giving us both the trigger for Alzheimer’s and the cure for it all in one,” says Lopera. “These two patients carry a gene that causes Alzheimer’s and at the same time another gene that protects them from the symptoms of dementia for decades to come.” in the so-called reelin gene. This plays an important role in the function and development of brain cells.
In the man with the altered reelin gene, the gene variant caused a particularly large amount of the reelin protein to be produced. This ensured that less harmful tau fibrils accumulated in the brain cells of this patient. Because the protein slows down the phosphorylation of the tau protein, as studies have shown. This protective effect was particularly strong in the entorhinal cortex, a key region of the brain for learning processes and memory that is usually the first to be affected by Alzheimer’s, as the researchers found.
Potential starting point for therapies
“The protective gene variant described in this study opens up a new perspective on the Reelin protein and the development of Alzheimer’s,” says co-author Diego Sepulveda-Falla from the University Hospital Hamburg-Eppendorf (UKE). “The fact that a gene protects against the development of Alzheimer’s disease can form an important basis for future therapy studies.”
The research team now plans to look for other possible carriers of protective mutations in the families of the two previously known patients. At the same time, they want to research whether and how the knowledge about the Reelin mutation can be used for a therapeutic approach against Alzheimer’s. If this succeeds, this therapy could then also help those affected by Alzheimer’s without the disease-causing Paisa mutation.
Source: University Medical Center Hamburg-Eppendorf, Massachusetts General Brigham
Von Nadja Podbregar