Taipei, Taiwan – New plasma biomarker tests for amyloid-β (Aβ) and tau protein may hold promise for a more convenient, safer, and less expensive method for detecting risk of developing Alzheimer's disease (AD), new research suggests.
The new tests are based on immunomagnetic reduction, in which magnetic particles are coated with antibodies to the biomarkers and the reduction in the spin of the particles correlates with the amount of ligand bound to them, Charles Shieh-Yueh Yang, PhD, reported here at the Alzheimer's Disease International (ADI) 28th International Conference.
Dr. Yang is professor at the Institute of Electro-optical Science and Technology at National Taiwan Normal University and president of MagQu, the developer of the new tests. He said further validation of the ability of the tests to differentiate stages of AD is needed, and he is aiming for a target of 1000 tests, which may require collaborations outside of Taiwan to get enough participants.
Current diagnosis of AD is based on expensive imaging tests — MRI, computed tomography, and positron emission imaging — that are time consuming and costly and have low efficiency and specificity, Dr. Yang told delegates. Alternatively, molecular detection of elevated concentrations of Aβ-40, Aβ-42, or tau in cerebrospinal fluid (CSF) require lumbar puncture and detection by multistep enzyme-linked immunosorbent assays.
In contrast, the new tests under development detect the spin of antibody-coated magnetic particles in an alternating current field. The antibodies are specific for Aβ-40, Aβ-42, or tau. When the particles bind ligand, they stick together to form clusters, inhibiting their spin. Electronic detectors can detect the amount of spin.
These sensitive methods allow the detection of the biomarkers in blood, where their concentrations are much lower than in CSF. The lower detection limits are 1 to 10 pg/mL for the Aβs and 0.1 to 1 pg/mL for tau.
In tests of human plasma measuring the ratios of Aβ-42 to Aβ-40, the method showed a continuum from normal (n = 66) to mild cognitive impairment (n = 21) to AD (n = 46).
With a cutoff ratio of 0.325, the test had a sensitivity of 94% and a specificity of 91%. When a tau plasma concentration cutoff of 23.89 pg/mL was used, that test had a sensitivity of 97% and a specificity of 91%.
Dr. Yang concluded that these tests have high sensitivity and specificity and look promising for assaying biomarkers of AD in plasma instead of in CSF. He said each test would cost about $50.
In response to a question from the audience of how the tests could be applied, he suggested the tau assay as a first screening test. "If the tau concentration is too high...you can do the [Aβ]-42 and the -40 detection," he said. If AD is strongly suspected, such as in a familial situation, he added, "I would like to suggest just to do the -42 and the -40 [tests]."
Biomarker Accuracy "Questionable"
Session co-chair Brian Draper, MD, from the School of Psychiatry at the University of New South Wales in Sydney, Australia, and chair of the Australian government’s Psychogeriatric Care Expert Reference Group, who was not connected with the study, commented to Medscape Medical News that plasma testing is desirable because of its convenience for patients but that "the state of play at the moment with plasma tests is that their accuracy is questionable for use as biomarkers in Alzheimer's disease, and that's really where the [cerebrospinal fluid tests] take over."
Considering that there are no effective preventive or therapeutic interventions for AD, Dr. Draper said, "I do minimal biomarker work at this point because I don't think I can tell people anything too much useful at this point. There are others who go the opposite, who do a lot of biomarker work, and the question becomes what do patients want to hear?"
He said the field is at a critical point, where potential preventive treatments will require tools for earlier diagnosis and where sensitive and specific biomarkers are being developed that will require effective treatments to be clinically useful as predictors of disease risk.
Dr. Yang is president of MagQu Co Ltd, the manufacturer of the test. Dr. Draper has disclosed no relevant financial relationships.
Alzheimer's Disease International (ADI) 28th International Conference. Abstract #OC074. Presented April 20, 2013.
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Cite this: Sensitive Test Detects Alzheimer's Biomarkers in Plasma - Medscape - Apr 23, 2013.