Alzheimer's blood test predicts beta-amyloid in the brain
Australian and Japanese scientists have discovered plasma biomarkers that can predict beta-amyloid deposition in the brain — the earliest pathological signature of Alzheimer’s disease.
Published in the journal Nature, their research has resulted in the creation of a minimally invasive blood test for the disease, with the potential to massively ramp up the pace of Alzheimer’s drug trials.
Beta-amyloid is an abnormal peptide and hallmark of Alzheimer’s disease that begins to build up in the brain about 30 years before any outward signs of dementia manifest. But current tests for beta-amyloid are expensive and invasive, such as brain scans with radioactive tracers and analysing spinal fluid taken via a lumbar puncture.
As a result, diagnosis is usually made without these tools, by assessing a patient’s range of symptoms. There is, therefore, an urgent need for a more cost-effective and less-invasive diagnostic tool to diagnose patients sooner and with better accuracy.
“Progress in developing new therapeutic strategies for Alzheimer’s disease has been disappointingly slow,” said Professor Colin Masters from The Florey Institute of Neuroscience and Mental Health and The University of Melbourne, who co-led the new research. “None of the three drugs currently on the market treat the underlying disease. New drugs are urgently required, and the only way to do that is to speed up the whole process.
“That requires trials with rigorous and economical patient selection, to avoid recruiting patients who may not even have Alzheimer’s disease. Due to the long timespans involved, pharmaceutical companies require accurate predictions of who is most at risk.”
The new test was the result of an extensive international collaboration, with the key technology, known as IP-MS (immunoprecipitation with mass spectrometry), developed by Shimadzu Corporation in Japan. Blood samples from patients in a large study from the Japanese National Center for Geriatrics and Gerontology (NCGG) were analysed to identify the relevant peptides, then tested against patient samples from the Australian Imaging, Biomarker and Lifestyle Study of Aging (AIBL) in order to validate the results.
“From a tiny blood sample, our method can measure several amyloid-related proteins, even though their concentration is extremely low,” said Shimadzu’s Dr Koichi Tanaka, who was instrumental in developing the initial blood testing procedure — and won the 2002 Nobel Prize in Chemistry as a result.
The researchers showed that the ratios of the different beta-amyloid-associated peptide fragments and a composite score can predict the level of beta-amyloid deposition in an individual’s brain. Their blood test can thus inform scientists with 90% accuracy if a patient has the very earliest stages of Alzheimer’s disease.
“Our study demonstrates the high accuracy, reliability and reproducibility of this blood test, as it was successfully validated in two independent large datasets from Japan and Australia,” said the leader of the Japanese team, Professor Katsuhiko Yanagisawa from NCGG.
The researchers suggest that their blood test has several potential applications. For example, clinical trials of disease-modifying therapies for Alzheimer’s disease are expected to be most effective when patients are at the earliest stages of the disease; the test may thus aid with the selection of suitable clinical trial participants. It could also potentially be used for population screening to identify at-risk individuals, although the authors note that its usefulness as a monitoring tool remains to be evaluated.
“This new test has the potential to eventually disrupt the expensive and invasive scanning and spinal fluid technologies,” said Professor Masters. “In the first instance, however, it will be an invaluable tool in increasing the speed of screening potential patients for new drug trials.”
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