Preliminary Study for a Multicenter Study of Alzheimer's Disease Cerebrospinal Fluid Biomarkers

Abstract

Background: The usefulness of cerebrospinal fluid (CSF) concentrations of amyloid beta protein 1-42 (Aβ42), phosphorylated tau (pTau) and total tau (tTau) have been increasing in Alzheimer’s disease (AD). However, the direct adoption of previously reported standard values is not appropriate due to interlaboratory variability. We started this study to set up an accessible system to measure CSF biomarkers in our country with high reproducibility and validity. Methods: Including CSFs from four different institutes the levels of Aβ42, pTau181 and tTau were measured in one lab. The intertest variability and difference in the levels of biomarkers depending on diseases were assessed. Through analysis of receiver operating characteristic cut points and binary logistic regression the cut-off values of Aβ42, pTau and tTau level were obtained, and their validity was evaluated. Results: The intertest consistency was high in measuring CSF biomarkers. The value of Aβ42 was markedly decreased in AD (n= 17) and other dementia (n= 9) compared to normal control (n= 12). The levels of pTau181 and tTau were high in AD, but not in other dementia and normal control. The threshold values of Aβ42, pTau181 and tTau were 290.3 pg/mL, 54.3 pg/ mL, and 320.7 pg/mL in differentiating AD from normal control showing high sensitivity and specificity. Especially, the ratios of pTau181/Aβ42 (> 0.16) and tTau/Aβ42 (> 0.76) showed the prime validity. Conclusions: Our data of CSF Aβ42, pTau181, and tTau levels were highly reproducible. PTau181/Aβ42 and tTau/Aβ42 ratios were the greatly helpful in differentiating AD from normal control.