For years, people with a family history of Alzheimer’s
disease have shied away from genetic testing, which
However, new research has highlighted a potential pathwayfor 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
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.
Source : foxnews.com
Source : foxnews.com
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