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Nobel-winning tech spots Alzheimer's risk factor

Japanese laureate helps develop a test that requires only a bit of blood

Koichi Tanaka, left, senior fellow at Shimadzu, and other researchers meet reporters at the Ministry of Health, Labor and Welfare on Jan. 29. (Photo by Wataru Ito)

TOKYO -- Researchers in Japan have announced a major step in the fight against Alzheimer's disease, with a new diagnostic method that requires only a small amount of blood. The breakthrough could spur the development of treatments for the disease, which accounts for 60-70% of dementia cases.

The researchers work for Japanese public and private entities, including the National Center for Geriatrics and Gerontology and Shimadzu. Among them is Koichi Tanaka, a senior fellow at Shimadzu, who won the Nobel Prize in chemistry in 2002.

Alzheimer's damages nerve cells and reduces their number, resulting in problems with memory and loss of cognitive abilities related to time and place. Generally, researchers believe the disease is caused by the buildup of two abnormal proteins. One is amyloid-beta, which begins accumulating in the brain more than 20 years before Alzheimer's shows up and creates senile plaque -- microscopic masses of fragmented and decaying nerve terminals -- outside the nerve cells.

The other protein is called tau. The accumulation of tau within nerve cells creates neurofibrillary tangles, which look like tangles of yarn, and kills the cells.

The new diagnostic method checks for the buildup of amyloid-beta, using fractions of the protein that are barely detectable in blood. The method is based on a highly accurate mass spectrometry technique devised by Tanaka and American scientist John B. Fenn, who shared the Nobel honors.  

Mass spectrometry is a technique for ionizing proteins and other macromolecules and electronically discharging them to find differences in their movements caused by differences in their mass. The differences make it possible to differentiate macromolecules of minutely different sizes. Tanaka and the other researchers paved the way for analyzing proteins in tiny amounts with this technique.

The research team has raised the accuracy of diagnoses by comparing the ratios of fractions of different types. Only 0.5cc of blood is needed to identify the buildup of amyloid-beta, they said.

The team tested the new method by using blood from seniors in Japan and Australia -- some with Alzheimer's and some with no health concerns. Using brain imaging, the team confirmed that the method is capable of diagnosing the buildup of amyloid-beta with 90% accuracy.

The accumulation of amyloid-beta is currently detected using positron emission tomography, or PET scans, or through painful examinations of cerebrospinal fluid extracted by a needle. PET scan-based examinations cost thousands of dollars. 

The blood-based diagnostic method might be a game changer, though there are some caveats. Pharmaceutical companies around the world have been striving to develop new drugs to reduce the accumulation of amyloid-beta in the brain, but have confirmed few effective candidates. To complicate matters, in some cases the accumulation of the protein does not cause Alzheimer's.

Some researchers are even starting to question whether amyloid-beta buildup actually causes Alzheimer's.

The equipment needed for the mass spectrometry technique is also costly, which means that less-expensive, more user-friendly equipment will be needed if the method is to make it into ordinary hospitals. 

Nevertheless, there is growing momentum toward identifying and treating risk factors before symptoms appear. The hope is that early countermeasures could stop the disease in its tracks. Painless examinations are crucial for prevention.

Alzheimer's is becoming a serious problem not only in developed countries, such as Japan, the U.S. and European nations, but also in China, India and other emerging markets. "We hope the new technology can contribute to the health and longevity of people around the world," Tanaka said. 

There has been progress on the tau front as well. A research team at Kyoto Prefectural University of Medicine announced in 2017 the development of a method to accurately detect phosphorylated tau using a blood test. The research was funded by the Japan Agency for Medical Research and Development.

Accumulations of abnormal tau proteins often appear later than amyloid-beta and there seems to be a correlation between the locations of the accumulated tau and how symptoms arise. For example, memory disorders are found in people with tau protein accumulations around the hippocampus, which is essential for memory function.

As a result, researchers increasingly believe tau is more directly related to Alzheimer's and should be a target for drug development.

Either way, as countries scurry to tackle the Alzheimer's problem, both amyloid-beta and tau are likely to get plenty of attention in labs.

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