A critical step toward determining eligibility for experimental and clinical treatment with anti-amyloid therapies in Alzheimer’s disease (AD) is to select appropriate subjects having a high likelihood of being Aβ+. We propose a clinical biomarker composite score, named Clinical β-Amyloid Positivity Prediction Score Plus (CAPS Plus), for Aβ+ prediction in people presenting with clinical Alzheimer’s syndrome including both prodromal and mild AD.

The original CAPS incorporated scores from the neuropsychiatry inventory questionnaire, mini-mental state examination score loss per year and Fazekas score. Plasma p-tau-217, a novel addition to CAPS, was measured using the Simoa HD-X with the AlzPATH p-tau217 Advantage Plus assay. To incorporate p-tau-217 into CAPS Plus, an intra-cohort cut-off (>0.698 pg/ml) for p-tau217 was generated using logistic regression and Yoden’s index. CAPS Plus had a maximum score of 5, with those ≥4 indicating a high probability of being Aβ+. The accuracy of CAPS Plus was computed through logistic regression and area under the receiver operating characteristic curve (AUROC) analysis.

Of n = 44 patients, n = 25 (57%) were Aβ+. Plasma p-tau-217 was significantly higher in the Aβ+ subgroup (1.36 vs 0.46 pg/mL, p < 0.0001). The AUROC was 0.89 for a CAPS Plus score of 4 or more, suggesting excellent discrimination and improving the accuracy of the original CAPS (0.86). CAPS Plus has a notably better specificity (89%) than the original CAPS (80%) and p-tau-217 alone (74%).

CAPS Plus is potentially a useful screening tool for enrollment in anti-Aβ therapy and clinical trials for AD, specifically addressing people with prodromal and mild AD.