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Can We Prevent Alzheimer’s by Targeting the Gene That Starts It?

Scientists have discovered a specific Alzheimer’s gene appears to drive the first appearance of amyloid plaque in the brain. Now they’re working on therapies targeting that gene to prevent the disease from developing. Learn more.


Some variants of the gene, RBFOX1, appear to increase the concentration of protein fragments that make up these plaques and may contribute to the breakdown of critical connections between neurons, another early sign of the disease.

The finding could lead to new therapies that prevent Alzheimer’s and better ways of identifying people with the greatest risk of developing the disease.

Background

In recent years, amyloid PET brain imaging has helped to reveal that the earliest signs of Alzheimer’s disease — deposits of amyloid in the brain — appear as early as 10 or 15 years before any symptoms of the disease become apparent.

But aside from the few cases caused by rare, inherited genes, researchers have been searching for the cause of excessive accumulation of amyloid in the brain of Alzheimer’s patients.

The hunt for genes

To find genes that drive EARLY amyloid accumulation, the new study examined the genomes of thousands of people whose PET images revealed amyloid deposits in the brain but who had not yet developed Alzheimer’s symptoms.

“By studying people with the earliest signs of Alzheimer’s, we can find genes that are unequivocally related to the start of disease. And these genes are more likely to lead to therapies that can prevent the disease from developing,” says Richard Mayeux, MD, chair of neurology at Columbia University Vagelos College of Physicians and Surgeons, who led the study.

What’s new

The study looked through the genomes of nearly 4,300 people who did not have Alzheimer’s but whose brains already contained variable amounts of amyloid plaque, as measured by PET imaging using amyloid tracers.

A genetic analysis uncovered a link between the appearance of amyloid deposits and APOE, a known Alzheimer’s gene, and a novel gene, RBFOX1.

About 10% of people in the study (predominantly with European ancestry) had RBFOX1 variants that were linked with the emergence of amyloid deposition.

Lower amounts of RBFOX1 in the brain appeared to be associated with increased amyloid and global cognitive decline during life.

Why it matters

Uncovering exactly how RBFOX1 regulates amyloid plaque could lead to ways to prevent plaque accumulation. Previous research has already suggested RBFOX1 is involved in the formation of amyloid precursors and the breakdown of synapses between neurons.

The connection between RBFOX1 and amyloid plaques may be relatively easy to untangle, unlike the well-known connection between APOE4 and amyloid, which is still not understood after decades of research.

“I think we’re going to find that these markers of eventual disease are where real progress can be made against Alzheimer’s,” Mayeux says. “It will be virtually impossible to change the disease course at the time symptoms appear. By then, the disease has already flourished for 10 to 15 years.”

“If we can target the genes that get amyloid started — and correct those problems somehow — we may be able to prevent the disease.”

SOURCE:

REFERENCE:

  • Neha S. Raghavan, Logan Dumitrescu, Elizabeth Mormino, Emily R. Mahoney, Annie J. Lee, Yizhe Gao, Murat Bilgel, David Goldstein, Theresa Harrison, Corinne D. Engelman, Andrew J. Saykin, Christopher D. Whelan, Jimmy Z. Liu, William Jagust, Marilyn Albert, Sterling C. Johnson, Hyun-Sik Yang, Keith Johnson, Paul Aisen, Susan M. Resnick, Reisa Sperling, Philip L. De Jager, Julie Schneider, David A. Bennett, Matthew Schrag, Badri Vardarajan, Timothy J. Hohman, Richard Mayeux. Association Between Common Variants in RBFOX1, an RNA-Binding Protein, and Brain Amyloidosis in Early and Preclinical Alzheimer Disease. JAMA Neurology, 2020; DOI: 10.1001/jamaneurol.2020.1760
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B. Berger

B. Berger

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Welcome

This site was inspired by my Mom’s autoimmune dementia.

It is a place where we separate out the wheat from the chaffe, the important articles & videos from each week’s river of news. With a new post on Alzheimer’s or dementia appearing on the internet every 7 minutes, the site’s focus on the best information has been a help to many over the past 15 years. Thanks to our many subscribers for your supportive feedback.

The site is dedicated to all those preserving the dignity of the community of people living with dementia.

Peter Berger, Editor

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