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Exciting Breakthrough in Alzheimer’s Research: New Treatment for Genetic Risk on the Horizon
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- Alzheimer’s disease is the commonest form of dementia, causing up to 70% of the 55 million dementia cases worldwide.
- Around half of those who develop Alzheimer’s disease have a variant of one gene — APOEe4— that increases the risk of developing the condition.
- This gene variant prevents cells clearing the beta-amyloid plaques that are characteristic of Alzheimer’s disease.
- Now, a study in nematodes and mice has identified a molecule that can inhibit APOEe4 and allow the cells to clear these beta-amyloid deposits, and potentially alleviate Alzheimer’s disease symptoms.
With an aging global population, dementia is a growing concern worldwide. A recent forecast by
Of these dementia cases, according to the
For dementia, the greatest risk factor is aging — with the likelihood of developing dementia increasing each year
Genetics can also influence whether a person develops dementia: About 1% of cases of Alzheimer’s disease are entirely caused by genes, and other genes increase the risk of developing Alzheimer’s.
The gene that expresses
Dr. Emer MacSweeney, CEO and medical director at Re:Cognition Health, told Medical News Today:
“In 2018, it was shown those with an APOEe4 gene are less able to clear waste products from the brain and, therefore, more susceptible to building up toxic levels of amyloid and tau protein, which is the hallmark of Alzheimer’s disease. The toxic amyloid and tau protein relentlessly destroy further brain cells, with the progression of the characteristic symptoms of [Alzheimer’s disease].”
Now, a team led by researchers at the University of Arkansas for Medical Sciences have found a molecule that binds to APOEe4and inhibits its harmful effects. They suggest it may form the basis for a new treatment for Alzheimer’s disease with a genetic basis.
The research is published in Communications Biology.
Dr. MacSweeney, who was not involved in the research, welcomed the study.
She said: “This study focuses on the role of the APOE gene, specifically the APOEe4. The research combines genetic association studies, cellular mechanism investigations, computational modelling, and experimental validation.”
Studies have shown that APOEe4 has several effects, including
This latest study found that APOEe4 blocks genes responsible for
When beta-amyloid builds up it forms plaques on and around nerve cells, which is thought to drive the cognitive impairment and other symptoms that are characteristic of Alzheimer’s disease.
The researchers used in vitro and in vivo models in both
In molecular models, they first identified the site on DNA where APOEe4 binds to inhibit autophagy. They then investigated molecules that could block this region to prevent APOEe4 binding, allowing autophagy of beta-amyloid to continue.
One molecule — CBA2 — bound to a stable “pocket“ region on APOEe4, blocking its activity.
Dr. Heather M. Snyder, Ph.D., Alzheimer’s Association vice president of Medical and Scientific Relations, not involved in this study, commented on its findings, noting that:
“It is exciting to see advances in technology that may accelerate therapy discovery. And it is exciting that this newly announced research is looking at a novel and understudied therapeutic target — APOEe41. Animal study potential new treatment
2. Animal study potential treatment options.
