Accuracy of plasma Abeta40, Abeta42, and p-tau181 to detect CSF Alzheimer's pathological changes in cognitively unimpaired subjects using the Lumipulse automated platform

Abstract

Background The arrival of new disease-modifying treatments for Alzheimer’s disease (AD) requires the identifca tion of subjects at risk in a simple, inexpensive, and non-invasive way. With tools allowing an adequate screening, it would be possible to optimize the use of these treatments. Plasma markers of AD are very promising, but it is neces sary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fuid or PET imaging. With this research, we want to evaluate the performance of plasma Aβ40, Aβ42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods Both plasma and CSF Aβ40, Aβ42, and p-tau181 have been evaluated in a group of 208 cognitively unim paired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the diferences in plasma marker values according to amyloid status (A−/+), AD status (consider ing AD+subjects to those A+plus Tau+), and ATN group defned by CSF. Finally, ROC curves have been performed, and the area under the curve has been measured using amyloid status and AD status as an outcome and diferent combinations of plasma markers as predictors. Results Aβ42, amyloid ratio, p-tau181, and p-tau181/Aβ42 ratio correlated signifcantly between plasma and CSF. For these markers, the levels were signifcantly diferent in the A+/−, AD+/−, and ATN groups. Amyloid ratio pre dicts amyloid and AD pathology in CSF with an AUC of 0.89. Conclusions Plasma biomarkers of AD using the automated Lumipulse platform show good diagnostic performance in detecting Alzheimer’s pathology in cognitively unimpaired subjects.