# Plasma p-tau217, p-tau181, and Aβ42 Predicts Amyloid PET Positivity in Cognitively Unimpaired Adults

## TL;DR

This study shows that blood levels of p-tau217 and other biomarkers can accurately predict amyloid buildup in the brains of adults without cognitive issues.

## Contribution

The study demonstrates that combining plasma p-tau217 with other biomarkers and clinical factors improves prediction of amyloid PET positivity.

## Key findings

- Plasma p-tau217 alone had an AUC of 0.85 for predicting Aβ PET status.
- A combined model with p-tau217, p-tau181, Aβ42, age, sex, and APOE ε4 achieved an AUC of 0.87.
- The combined model outperformed individual biomarkers in predicting Aβ PET positivity.

## Abstract

Early detection of Alzheimer's disease (AD) pathology in cognitively unimpaired individuals is critical for preclinical intervention. Plasma biomarkers, especially phosphorylated tau217 (p-tau217), are promising predictors of amyloid-β (Aβ) accumulation.

In this cohort study, we analyzed data from cognitively unimpaired older adults in the A4 and LEARN studies (n=1,407), comprising 452 participants with Aβ positron emission tomography (PET)-negative status and 955 participants with Aβ PET-positive status. We evaluated the accuracy of plasma biomarkers (p-tau217, p-tau181, Aβ42/40 ratio, and others) in predicting Aβ PET positivity using receiver operating characteristic analysis, comparing models with biomarkers alone versus those combined with covariates (age, sex, apolipoprotein E [APOE] ε4 genotype).

Plasma p-tau217 showed the strongest individual association with Aβ PET status (area under the curve [AUC] 0.85). A combined model integrating p-tau217, p-tau181, Aβ42, age, sex, and APOE ε4 achieved the highest diagnostic accuracy (AUC 0.87), significantly outperforming individual biomarkers.

Plasma p-tau217, particularly when combined with other biomarkers and clinical covariates, provides a robust method for predicting Aβ PET positivity in cognitively unimpaired older adults. This biomarker profile could enhance preclinical trial screening by identifying individuals likely to harbor Aβ pathology, potentially reducing the need for confirmatory PET scans.