Plasma p-tau217 Effectively Pre-Screens for Amyloid-β Positivity in Alzheimer Disease

A new multicenter study demonstrated plasma phosphorylated (p-tau)217's ability to recognize amyloid-β (Aβ)-PET positivity in cognitively unimpaired (CU) patients, providing support of its use as a stand-alone biomarker, or as an initial step prior to cerebrospinal fluid (CSF) biomarkers, for pre-screening in preclinical AD clinical trials. Overall, positive predictive values (PPVs) using p-tau217 reached 81%, which researchers noted could be further improved up to 95% with subsequent CSF measures.¹

Investigators included 1471 CU patients from 8 cohorts that had available data on the plasma p-tau217, Aβ CSF biomarkers, and Aβ-PET status. Researchers had plasma p-tau217 concentrations z-scored according to Aβ-negative participants and coordinated across cohorts using neuroCombat. Authors had cut-offs for plasma p-tau217 derived in the BioFINDER-1 cohort (n = 104) derived from different specificity levels to optimize PPVs (90%, 95%, and 97.5%).

The cut-offs were then used in the other cohorts to evaluate accuracy of plasma p-tau217 for the detection of Aβ-PET positivity. Among the plasma-positive participants only, investigators then assessed the value of dichotomized Aβ CSF, based on clinical thresholds, for evaluating Aβ-PET positivity. All of the models in the study included age and APOE-ε4 carriership as the covariates.

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Presented at the 2024 Alzheimer’s Association International Conference, July 28 to August 1, in Philadelphia, Pennsylvania, investigators noted that 334 (24.4%) of participants in the study were Aβ-PET positive. Using the a priori defined cutoffs, researchers reported that plasma p-tau217 categorization showed high PPVs (72.9%-81.2%), negative predictive values (NPVs, 82.5%-86.2%), and accuracy (82.4%-83.8%), revealing an overall rate of positivity between 10.9%-18.1%.

“If these numbers hold up and are replicated and confirmed by other independent labs, this approach may reduce the need for lumbar punctures and PET scans for Alzheimer diagnosis by 80% or even 90%,” lead author Gemma Salvadó, PhD, an associate researcher at Lund University, said in a statement.² “Our results support that plasma p-tau217 positivity alone may be sufficient as a selection of cognitively unimpaired, amyloid-positive participants for many clinical trials.”

In a second step when researchers applied CSF biomarkers to the plasma-positive patients, the PPVs increased up to 90.8%-95.3%, with NPVs ranging between 82.8%-86.7% and accuracies between 84.0%-87.3%. Findings also showed a slight reduction in the proportion of overall positive cases, 9.3%-14.3% from the original sample, given that the CSF positivity in the plasma-positive patients ranged between 79.4%-85.2%.

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REFERENCES
1. Salvadó G, et al. Use of plasma p-tau217 as a pre-screening method for detecting amyloid-PET positivity in cognitively unimpaired participants: A multicenter study. Presented at: 2024 Alzheimer’s Association International Conference; July 18 to August 1; Philadelphia, Pennsylvania. Abstract 85773.
2. Alzheimer’s Disease Blood Tests Could Improve Diagnosis in Primary Care, Speed Recruiting for Research, and Reduce Wait Times. News Release. Alzheimer’s Association. Published July 28, 2024. Accessed July 31, 2024.