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CTAD 2022 | Clinical robustness of CSF pTau/Aβ42 ratio for Alzheimer’s disease diagnosis

Cerebrospinal fluid (CSF) amyloid-β 1-42/amyloid-β 1-40 (Aβ42/Aβ40) and phosphorylated tau (pTau)/Aβ42 biomarker ratios have been shown to perform equally in their concordance with amyloid-PET in cognitively impaired individuals. Despite this, these biomarkers tolerate measurement variability to a different extent, which is important for the clinical application of such biomarkers. To test the clinical robustness of each biomarker, Henrik Schinke, PhD, Roche Diagnostics Europe, Penzberg, Germany, and his team simulated changes in bias (±10%) that would be expected in routine clinical use and compared how this affected the biomarkers’ concordance with amyloid-PET status, assessed via positive percent agreement (PPA) and negative percent agreement (NPA). In response to theoretical bias adjustment, pTau/Aβ42 demonstrated less change in NPA and PPA and a lower rate of reclassification (1.4%), compared to Aβ42/Aβ40 (10.5%). This suggests that in routine clinical use, pTau/Aβ42 will likely have a greater diagnostic performance and a lower risk of misclassification for people with borderline results. This interview took place at the Clinical Trials on Alzheimer’s Disease Congress 2022 in San Francisco.

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