“Even in a difficult-to-diagnose, real-world population of patients with MCI/dementia of unknown etiology, the combined test demonstrated outstanding performance,” Braunstein said. Combining this tau ratio with the Aβ42/40 ratio achieved an AUC of 0.96, although that was not significantly higher than the p-tau217/tau217 ratio alone. Accuracy climbed to 0.95 when the ratio of phosphorylated to unphosphorylated tau at this residue was measured instead of the concentration p-tau217 alone. On its own, plasma p-tau217 outperformed the Aβ ratio test, with an AUC of 0.92. C2N has a mass spec test for p-tau217 and, at AAIC, West reported how it performed alone or in combination with Aβ42/40 in PARIS-IDEAS. As many presentations at AAIC made clear, the plasma concentration of various phospho-tau species, including p-tau181, 217, and 231, are sensitive detectors of brain amyloid plaques, not of tau tangles as seen by PET. According to an August 23 press release, the company has joined forces with Eisai, Inc., to market blood biomarker tests in traditionally underserved communities.Ī bigger improvement was to be had by adding plasma p-tau217. C2N is currently marketing this combined test to dementia specialists. This combination of age, plasma Aβ42/40, and ApoE prototype-sold as PrecivityAD TM-yields an amyloid probability score.
As in previous evaluations of this test, including a measure of age and ApoE prototype-the latter measured by mass spec-nudged up the AUC significantly, to 0.86 in this cohort. For this reason, the lower AUC of plasma Aβ42/40 in the PARIS-IDEAS came as no surprise, C2N’s Joel Braunstein told Alzforum. In contrast, most research cohorts include people who participate in longitudinal aging studies, enabling a clearer delineation of persons who are healthy from those who have MCI, or dementia due to AD. Why the dip? IDEAS enrolls Medicare patients whose physicians have deemed them “difficult to diagnose,” making them candidates for amyloid PET. In the PARIS-IDEAS cohort, the blood test predicted amyloid-PET positivity with an AUC of 0.79, the researchers recently reported ( Hu et al., 2022).
AUC is a combined measure of specificity and sensitivity in which 1.0 is the highest score. In prior research cohorts, C2N’s plasma Aβ42/40 ratio assay, a mass spectrometry test that is commercially available for order by dementia specialists, has predicted the likelihood of amyloid positivity with an area under the curve of above 0.9, West noted. All participants in PARIS have cognitive symptoms for 65 percent, their amyloid PET scan was positive. PARIS is a prospective add-on to the community-based Imaging Dementia–Evidence for Amyloid Scanning (IDEAS) study. Louis presented biomarker findings from 221 participants in the ongoing Plasma Test for Amyloidosis Risk Screening study. At least for the best-established biomarkers thus far, many of the data shown at AAIC focused on this third phase, as scientists tried out the most promising biomarkers in community cohorts. Exploration and clinical assay development comprised the first two, while in phase 3, the biomarkers are put to the test in retrospective studies using banked blood samples from longitudinal studies, including population-based cohorts that tend to be more heterogenous than typical research cohorts. Researchers agreed that different combinations of biomarkers may suit different clinical stages of disease, with fewer needed to detect amyloid as symptoms worsen.Ĭharlotte Teunissen of Amsterdam University Medical Center laid out a five-phase roadmap of biomarker development ( Part 1). Among p-tau assays, mass spectrometry-based tests came out on top, though a handful of immunoassays were not far behind. At the Alzheimer’s Association International Conference, held July 31-August 4 in San Diego, scientists presented new findings in more heterogenous community cohorts, and compared multiple assays head-to-head. Now, multiple such tests-particularly the Aβ42/40 ratio and several phospho-tau species-have proven to be quite exquisite detectors of amyloid plaques, at least among well-characterized research cohorts. Only five years ago, the advent of a blood test that would root out amyloid plaques lurking in a person's brain was just emerging on the horizon ( Jul 2017 news).
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