Optimal amyloid and tau CSF biomarkers for the detection of amyloid and tau PET positivity in a memory clinic population

Abstract

Accurate detection of Alzheimer’s disease (AD) pathophysiological changes is crucial for research and clinical practice. While positron emission tomography (PET) imaging is an established reference standard for detecting brain amyloid and tau deposition, cerebrospinal fluid (CSF) biomarkers offer a more accessible alternative. This study aimed to identify optimal CSF biomarkers and thresholds for predicting tau and amyloid PET positivity in a memory clinic population. This cross-sectional, observational study included 220 participants from a memory clinic who underwent amyloid or tau PET scans and CSF biomarker analysis using either Fujirebio INNOTEST or LUMIPULSE assays. CSF biomarker performance was assessed via receiver operating characteristic (ROC) analysis. Double-threshold approaches were implemented to address classification uncertainty. Ratios combining biomarkers of both amyloid and tau, such as Aβ42/pTau, consistently outperformed individual biomarkers in detecting amyloid and tau PET positivity. For amyloid PET, the Aβ42/pTau ratio achieved an AUC of 0.93 (95% CI: 0.86–0.99) with INNOTEST and an AUC of 0.89 (95% CI: 0.8–0.98) with LUMIPULSE. For tau PET, the Aβ42/pTau ratio achieved an AUC of 0.85 (95% CI: 0.77–0.93) with INNOTEST and an AUC of 0.97 (95% CI: 0.9-1.00) with LUMIPULSE. Double thresholds enabled classification based on predefined sensitivity and specificity, and can be used by clinicians to quickly assess a subject’s likelihood of positivity based on their biomarker levels. CSF biomarker ratios such as Aβ42/pTau provide high predictive accuracy for brain amyloid and tau deposition. Implementing double thresholds enhances clinical utility by highlighting ambiguous cases requiring further assessment.