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Alzheimer's Disease

New Alzheimer’s discovery could hold key to preventative treatments for high-risk patients

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For years, people with a family history of Alzheimer’s disease have shied away from genetic testing, which could reveal that they carry the ApoE4 protein – a genetic risk factor associated with a 10-fold higher chance of developing the incurable neurodegenerative condition.

However, new research has highlighted a potential pathway for early intervention methods that could help those at a high risk for Alzheimer’s, making genetic screening for the disease as important as cholesterol tests are to preventing heart disease.

Researchers from The Buck Institute for Research on Aging, an independent research association based in Novato, Calif., have long been interested in discovering why ApoE4 is associated with such a high risk for Alzheimer’s disease.  

“Why is this the dominant risk factor?” study author Dr. Dale Bredesen, founding CEO of the Buck Institute, told FoxNews.com. “Though people have known this for 20 years, it’s never been clear what it is that ApoE4 does to confer such risk.”

Prior research had focused on the discovery that ApoE4 appears to affect the clearance of amyloid-beta (A-beta), a plaque that builds up in the brains of patients with Alzheimer’s disease. However, Bredesen and his colleagues weren’t convinced that this finding told the whole story of why ApoE4 causes Alzheimer’s.

“Treating that hasn’t worked very well,” Bredesen said. “There’s an emerging feeling, which we believe, that this is more than just about A-beta.”

In a study published in The Proceedings of the National Academy of Sciences, Bredesen and his colleagues analyzed ApoE4 cell cultures and discovered that ApoE4 was also associated with a dramatic reduction in SirT1 - a protein associated with anti-inflammation, anti-aging and longevity.

Bredesen said that as SirT1 decreases, it affects a certain protein crucial to the storage or loss of memories – the amyloid precursor protein (APP).

“You have a molecule called the APP, present in neurons and most cells in your body, and at all times this APP is getting cleaved,” Bredesen said. “It turns out there are two alternative patterns. So it is a little bit like how the government can go on shutdown or active. APP can go in the direction of memory or forgetting.”

In Alzheimer’s, Bredesen says people are on the ‘wrong side’ of this process – causing them to forget rather than retain memories.

However, by maintaining SirT1 levels, researchers believe they may be able to prevent these proteins from going awry. As a result of their discovery, Bredesen and his colleagues attempted to identify drugs that might be able to maintain levels of SirT1 in ApoE4 cell cultures. So far, they have successfully identified four drugs that seem to be effective – though they have yet to test their findings in humans.

“It gives us a leg up on saying, ‘Okay, we can begin to look at how to treat people with ApoE4 even when they’re young to make sure they never get Alzheimer’s, by affecting that link between ApoE4and Alzheimer’s,’” Bredesen said.

Furthermore, Bredesen and his colleagues also performed experiments in which they successfully reinserted SirT1 proteins back into cells already affected by ApoE4. By doing this, they were able to correct the abnormalities present in the cell and return it to a healthy state. This led Bredesen and his colleagues to speculate that treatment might be possible even for those already entering the early stages of Alzheimer’s.

“Most people today don’t want to know if they have ApoE4 because what can they do about it? This could change the landscape where we say everyone should know, just like with high cholesterol or high blood pressure, because you can do something about it,” Bredesen said.