Combination p-tau217 and Aβ42/40 Blood Test Accurate for Detecting Alzheimer Disease in Clinical Settings

Study results presented at the 17th annual Clinical Trials on Alzheimer’s Disease (CTAD) conference demonstrated that combined mass spectrometry-based plasma Aβ42/40 and percentage of plasma phosphorylated tau217 (p-tau217) had high accuracy in identifying Alzheimer disease (AD) among individuals with cognitive symptoms in both primary and secondary care settings. Study authors noted that an accurate blood test for AD could streamline the diagnostic work-up and treatment for the condition, and future studies are needed to evaluate the test’s impact on clinical care.

The study included 1213 participants with cognitive symptoms (mean age, 74.2 years), of whom 48% were women, 23% had subjective cognitive decline, 44% had mild cognitive impairment, and 33% had dementia. Researchers used the Amyloid Probability Score-2 (APS2) to evaluate the diagnostic accuracy of percentage of plasma p-tau217 combined with plasma Aβ42/40 measured by mass spectrometry. The primary outcome was AD pathology determined by abnormal cerebrospinal fluid Aβ42/40 and p-tau217. The secondary outcome was clinical AD. Researchers applied blood biomarker cutoffs established in an independent cohort to primary (n=307) and secondary care (n=300) cohorts comprised of patients undergoing cognitive evaluation, and prospectively evaluated blood tests in primary (n=208) and secondary (n=398) care.

• Samples analyzed in a single batch in primary care had an area under the curve (AUC) for APS2 of 0.97 (95% CI, 0.95 to 0.99), a positive predictive value (PPV) of 91% (95% CI, 87 to 96%), and a negative predictive value (NPV) of 92% (95% CI, 87 to 96%)
• Samples analyzed in a single batch in secondary care had an AUC of 0.96 (95% CI, 0.94 to 0.98), PPV of 88% (95% CI, 83 to 93%), and NPV of 87% (95% CI, 82 to 93%).
• Samples analyzed prospectively (bi-weekly) in primary care had an AUC of 0.96 (95% CI, 0.94 to 0.98), PPV of 88% (95% CI, 81 to 94%), and NPV of 90% (95% CI, 84 to 96%)
• Samples analyzed prospectively in secondary care had an AUC of 0.97 (95% CI, 0.95 to 0.98), PPV of 91% (95% CI, 87 to 95%), and NPV of 91% (95% CI, 87 to 95%).
• Primary care physicians identified clinical AD correctly in 61% of patients (95% CI, 53 to 69%) after clinical examination, cognitive testing, and a CT scan vs 91% (95% CI, 86 to 96%) for APS2 (P<.001).
• Dementia specialists identified clinical AD correctly in 73% of patients (95% CI, 68 to 79%) vs 91% (95% CI, 85 to 95%) for APS2 (P<.001).  
• In the overall study population, the accuracy of APS2 (90%; 95% CI, 88 to 92%) was not significantly different from percentage of p-tau217 (90%; 95% CI, 88 to 91%).