Discovery Offers Hope for Diagnosis and Treatment of Alzheimer's

Researchers have made a discovery that offers new hope for the early diagnosis and treatment of Alzheimer's disease.

Alzheimer's leads to severe mental degeneration and almost-inevitable death, and there is no known cure, nor even a reliable technique for early diagnosis. A patient is diagnosed with advanced Alzheimer's in the United States every 70 seconds, and deaths due to Alzheimer's have increased by a staggering 47 per cent since 2000. With the Baby Boomer population aging, those numbers are expected to explode even further in coming decades.

There are more than 5.3 million people with Alzheimer's in the United States, and more than 300,000 in Canada. Every one of those patients faces years of increasing mental incapacity followed by almost certain death, with no hope of treatment. The U.S. Alzheimer's Association has called the current situation a "crisis."

Dr. Hemant Paudel and fellow researchers report that the addition of a single phosphate to an amino acid in a key brain protein is a principal cause of Alzheimer's. Identifying this phosphate, one of up to two-dozen such molecules, could make earlier diagnosis and treatment of Alzheimer's possible.

The crucial protein, called a tau protein, is a normal part of the brain and central nervous system. But in Alzheimer's patients, tau proteins go out of control and form tangles that, along with senile plaques, are the primary cause of the degenerative disease.

Several years ago, it was discovered that tau proteins in normal brains contain only three to four attached phosphates, while abnormal tau in Alzheimer's patients have anywhere from 21 to 25 additional phosphates.

Paudel and his team have discovered that it is the addition of a single phosphate to the Ser202 amino acid within the tau brain protein that is the principal culprit responsible for Alzheimer's.

"The impact of this study is twofold," said Paudel. "We can now do brain imaging at the earliest stages of the disease. We don't have to look for many different tau phosphates, just this single phosphate. The possibility of early diagnosis now exists. This discovery gives us, for the first time, a clear direction towards the early diagnosis and treatment of Alzheimer's."

Paudel and his students worked for years to exclude the phosphates not directly responsible for causing Alzheimer's symptoms. They finally succeeded by working with FTDP-17, a genetic disease with symptoms similar to Alzheimer's, but transmitted via mutations. By genetically manipulating these mutations, they were able to prove that the phosphate on Ser202 almost single-handedly is responsible for the tau abnormalities that cause both FTDP-17 and Alzheimer's.

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References:
1. Hemant Paudel, et al. McGill University.