Stability Performance of LiCA-Based Blood Biomarkers for Amyloid-β Positivity in the Expanded C-PAS Cohort

LiCA-based blood biomarkers demonstrate consistent diagnostic performance in the expanded C-PAS cohort. The p-tau217/Aβ42 ratio exhibits optimal accuracy (AUC=0.947), and the refined dual cut-off minimizes uncertain cases, supporting efficient Aβ positivity prediction with reduced reliance on PET-CT.

Alzheimer's disease (AD) is the leading cause of dementia, driven by amyloid-β (Aβ) plaque accumulation. Early detection of Aβ positivity is critical for timely intervention.

Blood Biomarkers for AD

Blood-based markers provide a minimally invasive alternative to CSF and PET:

• p-tau217: Phospho-tau

• GFAP: Astrocyte activation

• NfL: Neurodegeneration

• Aβ42/40: Amyloid ratio

Prior C-PAS Study

Our study (N=1,254) validated LiCA biomarkers. p-tau217 was top performer (AUC=0.941). Dual cut-off showed clinical utility.

Study Objective

Confirm stability in 180 additional participants and refine p-tau217 dual cut-off.

Study Design

Prospective validation. [18F]florbetapir PET-CT as reference.

Participants (N=180)

Aβ- (N=87), Aβ+ (N=93). 95% CI.

LiCA Assays

Six biomarkers: Aβ42/40, p-tau181, p-tau217, GFAP, NfL, p-tau217/Aβ42.

Analysis

AUC (95% CI); dual cut-off: ≤0.37, >0.47 pg/mL

• LiCA biomarkers demonstrate consistent diagnostic performance in the expanded C-PAS cohort, confirming external validity of prior findings.

• The p-tau217/Aβ42 ratio achieves optimal accuracy (AUC=0.947), outperforming standalone p-tau217 (AUC=0.933).

• The refined dual cut-off reduces the gray zone from 16% to 12% (sensitivity=0.92, specificity=0.93).

• These findings support the clinical use of LiCA assays for early AD screening with reduced PET-CT reliance.