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Spinal fluid test to spot Alzheimer's

Protein fragments called beta amyloid oligomers are present in cerebrospinal fluid

Houston: Scientists have developed a test that could predict the risk of developing Alzheimer's disease by detecting abnormalities in spinal fluid.

The test detects tiny, misfolded protein fragments called beta amyloid oligomers in cerebrospinal fluid taken from patients.

Scientists used to think amyloid plaques were the problem in Alzheimer's disease.

"Now it seems clear that the aggregates are not the main culprits, it's their precursors, so-called beta amyloid oligomers," said Claudio Soto of the University of Texas Medical School at Houston. "This is the key molecule and could be the best, most reliable way to make an early diagnosis," Soto said.

"Those beta amyloid oligomers may be circulating in the body for years if not decades before cognitive symptoms arise," Soto added.

In the new study, Soto and his colleagues applied a technology they developed earlier for detection of the misfolded proteins responsible for prion diseases including mad cow disease.

Their protein misfolding cyclic amplification (PMCA) technology works by amplifying existing misfolded proteins and then breaking them up into smaller pieces.

When mixed with the equivalent, normal protein, the misfolded fragments act as seeds for the formation, in the case of beta amyloid, of amyloid clumps like those found in the Alzheimer's brain.

The researchers showed that their PMCA technology can detect beta amyloid oligomers at incredibly low concentrations.

In principle, their earlier prion work suggests it might be possible to detect even a single particle of misfolded beta amyloid.

Most importantly, Soto and his colleagues were able to distinguish between patients with Alzheimer's disease and those with other neurodegenerative or neurological disorders with 90 per cent sensitivity and 92 per cent specificity by applying their test to cerebrospinal fluid samples.

The next step, Soto said, is to adapt the technology for use with blood or urine samples, which would be much easier to obtain for screening perfectly healthy people for biochemical signs of Alzheimer's disease.

If additional research can confirm the utility of the test in Alzheimer's and perhaps other conditions (eg Parkinson's disease), Soto said a US Food and Drug Administration-approved test could be on the market in as little as three years.

The findings were reported in the Cell Press journal Cell Reports.

( Source : PTI )
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