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Why Don’t We All Get Alzheimer’s Disease?

Nature plays a trick (August 7)

Researchers at the University of California–San Diego School of Medicine offer an explanation for why we all don’t get Alzeimer's disease (AD) — a trick of nature that in most people maintains critical separation between a protein and an enzyme that, when combined, trigger the progressive cell degeneration and death characteristic of AD.

Although one might think the brains of people who develop AD possess building blocks of the disease absent in healthy brains, for most sufferers this is not true. Every human brain contains the ingredients necessary to spark AD, but while an estimated 5 million Americans have AD — a number projected to triple by 2050 — the vast majority of people will not develop the devastating neurological condition.

For researchers, these facts produce a singular question: Why don’t we all get AD?

In a paper published in Neuron, Subhojit Roy, MD, PhD, and colleagues offer an explanation — a trick of nature that, in most people, maintains critical separation between a protein and an enzyme that, when combined, trigger the progressive cell degeneration and death that is characteristic of AD.

Creating beta-amyloid requires the convergence of amyloid precursor protein (APP) and an enzyme that cleaves APP into smaller toxic fragments, called beta-secretase (BACE).

“Both of these proteins are highly expressed in the brain,” said Roy, “and if they were allowed to combine continuously, we would all have AD.”

But that doesn’t happen. Using cultured hippocampal neurons, the researchers discovered that healthy brain cells largely segregate APP and BACE-1 into distinct compartments as soon as they are manufactured, ensuring that the two proteins do not have much contact with each other. “Nature seems to have come up with an interesting trick to separate co-conspirators,” said Roy.

The scientists also found that the conditions promoting greater production of beta-amyloid protein boost the convergence of APP and BACE.

Source: Medical Xpress; August 7, 2013.

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