As blood-based biomarkers move toward clinical use in Alzheimer’s disease, a head-to-head study has found that commercially available tests for phosphorylated tau at threonine 217 (p-tau217) do not all perform equally. The findings suggest that individual assays and analytical platforms may need to be evaluated and calibrated separately rather than treated as interchangeable tests.
Comparing nine p-tau217 assays
The Clinical Evaluation of Blood-Based Tests for the Rapid Identification of Amyloid Pathology in AD (CLEAR-AD) study included 431 participants from 10 memory clinics in China. The cohort included cognitively unimpaired individuals, patients with mild cognitive impairment, and patients with dementia.
Researchers analyzed blood samples at a central laboratory using nine commercially available p-tau217 assays across three analytical platforms. Results were compared with amyloid positron emission tomography (PET), which was used as the reference for detecting amyloid pathology.
Seven of the nine assays demonstrated strong accuracy for identifying amyloid PET positivity, while two showed substantially lower diagnostic discrimination. The findings indicate that the clinical performance of plasma p-tau217 testing can vary according to the specific assay and analytical platform.
Overview of the CLEAR-AD study evaluating the diagnostic accuracy of nine commercial plasma p-tau217 assays against amyloid PET imaging in a multicenter memory clinic cohort.
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Researchers also evaluated a two-cutoff approach intended to classify patients as likely positive or negative for amyloid pathology, leaving an intermediate group with inconclusive results. For the highest-performing assays, the strategy maintained high diagnostic certainty while limiting the proportion of intermediate results.
Adding plasma amyloid-beta measurements to create a biomarker ratio provided additional diagnostic benefit only in certain subgroups, including patients with mild cognitive impairment.
The study also found that manufacturer or previously published cutoff values performed differently when applied to this independent cohort. The findings therefore point to the importance of validating and calibrating thresholds for individual platforms before implementation in clinical practice.
As disease-modifying Alzheimer’s treatments increase the need for accessible diagnostic testing, high-performing plasma p-tau217 assays could potentially help streamline assessment of amyloid pathology. However, the results emphasize that assay selection, platform-specific calibration, and standardized testing protocols will be important considerations for laboratories adopting these biomarkers.
Note: This news summary was generated by AI based on a published press release, followed by a review from human editors.
