Cerebrospinal Fluid Biomarker Ratio Concordance with Amyloid Positron-Emission Tomography: A Diagnostic Test Accuracy...

Cerebrospinal fluid (CSF) biomarker ratios (amyloid-β [Aβ]42/Aβ40, phosphorylated-tau [pTau]/Aβ42, and total tau [tTau]/Aβ42) are lower-cost alternatives to amyloid positron-emission tomography (PET) for Alzheimer's disease diagnosis. Among these CSF biomarker ratios, it is not clear whether concordance with amyloid PET is highest with Aβ42/Aβ40, pTau/Aβ42, or tTau/Aβ42. To evaluate this, we conducted a diagnostic test accuracy meta-analysis.

Medline and Embase were searched for articles published between January 2008 and February 2026 reporting concordance of ≥ 1 CSF biomarker ratio with amyloid PET. Statistical analyses were performed using the bivariate model of Reitsma with the R package mada v0.5.11.

This quantitative meta-analysis comprised 38 studies, including a total of 7504 participants, with 35 studies available for statistical analysis. All three CSF biomarker ratios (Aβ42/Aβ40, pTau/Aβ42, and tTau/Aβ42) were highly concordant with amyloid PET. However, the pTau/Aβ42 ratio showed numerically higher overall percent agreement with amyloid PET positivity (90.4%) versus Aβ42/Aβ40 (89.5%) or tTau/Aβ42 (89.2%), a significantly higher area under the curve (0.955) versus Aβ42/Aβ40 (0.921, p value for difference 0.018), and a significantly lower false positive rate (0.116) versus Aβ42/Aβ40 (0.153, p value for difference 0.015).

pTau/Aβ42 showed the highest overall concordance with amyloid PET positivity and the lowest false positive rate versus Aβ42/Aβ40 or tTau/Aβ42.