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A commercially available plasma assay that measured phosphorylated tau at threonine 217 (p-tau217) accurately identified biological Alzheimer's disease, data from three cohorts showed.

Across all cohorts, the p-tau217 assay identified elevated amyloid-beta with an area under the curve (AUC) of 0.92-0.96 (95% CI 0.89-0.99), reported Nicholas Ashton, PhD, of Gothenburg University in Sweden, and co-authors in .

The amyloid findings were comparable with cerebrospinal fluid (CSF) biomarkers, the researchers said. The immunoassay also detected elevated tau pathology with an AUC of 0.93-0.97 (95% CI 0.84-0.99) across the cohorts.

"Notably, the assay demonstrated high accuracy in identifying tau pathology within amyloid-beta-positive individuals," Ashton and colleagues wrote. "This is particularly important as anti-amyloid therapies may be less effective in patients with advanced tau pathology."

Phosphorylated tau is a leading Alzheimer's blood biomarker candidate, showing better diagnostic accuracy and disease specificity than amyloid-beta tests or assessments of neurofilament light (NfL). High-performing p-tau tests have shown a substantial increase in Alzheimer's patients occurring concurrently with amyloid plaques. Several p-tau candidates have been tested and p-tau217 has shown good utility.

"With the imminent implementation of anti-amyloid-beta therapies in dementia management, validated blood biomarkers are urgently needed to guide timely treatment decisions," Ashton and co-authors noted. "While plasma p-tau217 has shown promise as a diagnostic tool for Alzheimer's disease, its widespread evaluation has been hindered by limited availability of commercial assays."

The researchers assessed a commercial p-tau217 test (ALZpath pTau217) developed on the single molecule array (Simoa) platform in blood. They evaluated its performance in three cohorts: the cross-sectional and longitudinal Translational Biomarkers in Aging and Dementia cohort (October 2017-August 2021) and Wisconsin Registry for Alzheimer's Prevention cohort (February 2007-November 2020), and the cross-sectional Sant Pau Initiative on Neurodegeneration cohort (baseline visits March 2009-November 2021).

The study included 786 people with and without cognitive impairment. Mean age was about 66 years and 64.1% were women. About a third of the study population was classified as cognitively impaired.

In all cohorts, plasma p-tau217 alone, or p-tau217 plus demographic variables such as age, sex, and APOE status, outperformed all other blood-based biomarkers -- including p-tau181, p-tau231, amyloid-beta 42/40, glial fibrillary acidic protein (GFAP), and NfL -- in predicting amyloid and tau status. Longitudinally, plasma p-tau217 values showed an annual increase only in amyloid-beta-positive individuals, with the highest increase observed in people with tau positivity.

A three-range approach recommended by which suggested confirmatory testing for patients with uncertain blood test results, showed that about 12% to 23% of participants needed advanced testing, depending on their clinical stage.

"The detection of abnormal amyloid-beta pathology using a three-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%," Ashton and co-authors observed.

The cohorts used in the study may not fully represent real-world settings, the researchers noted. "Importantly, the reported negative and positive predictive accuracy of these reference ranges can vary based on the prevalence of the outcome in the target population," they wrote.

This research demonstrates that a commercially available p-tau217 blood test can accurately identify individuals with amyloid and tau pathology and that cutoffs perform relatively consistently across cohorts, noted Suzanne Schindler, MD, PhD, of Washington University in St. Louis, who wasn't involved with the study.

"Additional studies are needed to validate this test in typical clinical cohorts, and to determine whether this assay performs accurately when samples are sent in many batches," Schindler told 麻豆传媒.

"Further, other studies have shown that p-tau217 levels can be affected by certain medical conditions, and guidance must be formulated on how to use these tests in patients with medical comorbidities," she added. "Notably, the ratio of phosphorylated to non-phosphorylated p-tau217 may be less affected by ."

The ALZpath plasma p-tau217 assay is used globally and will available in the U.S. later this month as a laboratory-developed test (LDT) known as ALZpath Dx under the Clinical Laboratory Improvement Amendments () program. ALZpath plans to submit the assay to the FDA as an in vitro diagnostic in 2025 or 2026, according to a company spokesperson.

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