Sunday, June 4, 2023

This genetic variant protected against Alzheimer’s for 30 years

A study published today in “Nature Medicine” provides insight into why some people may be more resistant to Alzheimer’s disease than others. Some people who have a mutation in the gene known to cause early-onset Alzheimer’s disease do not show symptoms of the condition until much later in life, much later than expected. The findings may lead to strategies for delaying or preventing the condition.

Identified mutation enhances protein’s function in reel And thus promotes the survival of neurons. This is a recently identified rare genetic variant of the RELN gene (encoding Reelin signaling protein) and which he says is associated with more than two decades of resistance to autosomal dominant Alzheimer’s disease (ADAD).

This is the second case of such resilience from a large family of more than 6,000 living members in Colombia who did not develop mild cognitive problems until nearly two decades after infancy. Harvard Medical School (USA) Joseph F. “The research discovers a new molecular pathway that could be a therapeutic target for increasing resilience in all forms of Alzheimer’s disease,” explains Arboleda-Velasquez. Work.

ADAD is a rare inherited form of Alzheimer’s disease, usually caused by specific mutations in genes. DOG1 encoding the transmembrane protein presenilin 1. It is characterized by the onset of cognitive impairment, such as memory loss, at an early age, usually around the age of 40–50.

The previous case involved a woman who had an E280A mutation in a gene called presenilin 1 (PSEN1), which causes early-onset Alzheimer’s disease.

They also had two copies of a genetic variation called Christchurch, named after the New Zealand town where it was first found in the APOE3 gene (APOE3ch). The woman is said to have remained without cognitive problems for almost 30 years after the expected age of onset, despite the fact that she also showed evidence of Alzheimer’s disease in the brain.

Francisco Lopera, Yaquiel T. Queiroz, Joseph F. The team, led by Arboleda-Velasquez and Diego Sepulveda-Fala, analyzed clinical and genetic data from 1,200 people in Colombia who carry PSEN1 mutations and are predisposed to ADAD.

Thus, they identified a man who, despite having a PSEN1 mutation for early-onset ADAD, remained cognitively intact until the age of 67.

The authors compared this individual to the case of a woman with ADAD. Both men showed extensive and considerable amyloid pathology in the brain, which is a pathological hallmark of Alzheimer’s disease.

However, Diego Sepulveda-Falla of the University Medical Center Hamburg-Eppendorf, (Germany) explains to ABC Salud, “There was limited aggregation of tau (a microtubule-stabilizing protein in the brain) in the entorhinal cortex, a region of the brain. Which is typically affected in the early clinical stages of Alzheimer’s disease.

The authors did genetic sequencing and found that this second individual had a different type of mutation: a new rare variant of RELN (H3447R called COLBOS).

Sepúlveda-Falla explains that this mutation “causes RELN ligand, a binding molecule, to be more effective in limiting tau aggregation, but more research is needed to ascertain this.”

The APOE and Reelin proteins involved in protecting these individuals act as ligands for common cellular receptors, and the authors indicate that this may suggest a common mechanism for Alzheimer’s resistance.

The findings uncover a previously unknown molecular pathway that may confer resilience to cognitive decline in people at increased risk of Alzheimer’s disease.

“There is currently a great need for more effective treatments against Alzheimer’s and this discovery points to a new therapeutic target that could provide protection for several decades,” he told ABC Salud. arboleda-velasquez,

The researchers conclude that studying these individuals may reveal new information about genetic variants that reduce the risk of developing Alzheimer’s disease and other forms of dementia.

Nation World News Desk
Nation World News Desk
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