Abstract: Background: The arrival of new disease-modifying treatments for Alzheimer's disease (AD) requires the identification 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 necessary to prove that alterations in their levels are related to alterations in gold standard markers such as cerebrospinal fluid or PET imaging. With this research, we want to evaluate the performance of plasma A?40, A?42, and p-tau181 to detect the pathological changes in CSF using the automated Lumipulse platform. Methods: Both plasma and CSF A?40, A?42, and p-tau181 have been evaluated in a group of 208 cognitively unimpaired subjects with a 30.3% of ApoE4 carriers. We have correlated plasma and CSF values of each biomarker. Then, we have also assessed the differences in plasma marker values according to amyloid status (A???/?+), AD status (considering AD?+?subjects to those A?+?plus Tau?+), and ATN group defined 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 different combinations of plasma markers as predictors. Results: A?42, amyloid ratio, p-tau181, and p-tau181/A?42 ratio correlated significantly between plasma and CSF. For these markers, the levels were significantly different in the A?+?/???, AD?+?/???, and ATN groups. Amyloid ratio predicts 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.

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