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DIAGNOSTIC ACCURACY OF PLASMA P-TAU217 FOR DETECTING PATHOLOGICAL CEREBROSPINAL FLUID CHANGES IN COGNITIVELY UNIMPAIRED SUBJECTS USING THE LUMIPULSE PLATFORM

F. Martínez-Dubarbie, A. Guerra-Ruiz, S. López-García, C. Lage, M. Fernández-Matarrubia, J. Infante, A. Pozueta-Cantudo, M. García-Martínez, A. Corrales-Pardo, M. Bravo, M. López-Hoyos, J. Irure-Ventura, E. Valeriano-Lorenzo, M.T. García-Unzueta, P. Sánchez-Juan, E. Rodríguez-Rodríguez

BACKGROUND: Plasma biomarkers of Alzheimer’s disease (AD), especially p-tau217, are promising tools to identify subjects with amyloid deposition in the brain, determined either by cerebrospinal fluid (CSF) or positron emission tomography. However, it is essential to measure them in an accurate and fully automated way in order to apply them in clinical practice. OBJECTIVES: To evaluate the diagnostic performance of the fully-automated Lumipulse plasma p-tau217 assay in preclinical AD. DESIGN: Cross-sectional analyses from a prospective cohort. SETTING: A population-based study. PARTICIPANTS: Volunteers over 55 years without cognitive impairment or contraindications for complementary tests. MEASUREMENTS: Plasma p-tau217 was measured with the fully-automated Lumipulse assay, as well as CSF Aβ40, Aβ42, p-tau181, and t-tau levels. We correlated plasma p-tau217 with CSF Aβ40, Aβ42 and p-tau181, and assessed the differences in plasma p-tau217 according to CSF amyloid status (A-/+), AD status (AD+ being those subjects A+T+ and AD- the rest) and ATN group. We performed ROC curves and measured the areas under the curve (AUC) using CSF amyloid as result, and both p-tau217 and ApoE4 status as predictor. RESULTS: We screened 209 cognitively unimpaired volunteers with a mean age 64 years (60-69) and 30.2% of ApoE4 carriers. Plasma p-tau217 correlated significantly with CSF Aβ42/Aβ40 (Rho=-0.51; p-value<0.001) and p-tau181 (r=0.59; p-value<0.001). Its levels were significantly higher in A+ subjects (0.26 pg/ml) compared with A- (0.12 pg/ml; p-value<0.001); and along ATN groups. It predicts CSF amyloid pathology with an AUC of 0.85. CONCLUSIONS: Plasma p-tau217 measured using the Lumipulse platform shows promise as an accurate biomarker of preclinical AD pathology.

CITATION:
F. Martínez-Dubarbie ; A. Guerra-Ruiz ; S. López-García ; C. Lage ; M. Fernández-Matarrubia ; J. Infante ; A. Pozueta-Cantudo ; M. García-Martínez ; A. Corrales-Pardo ; M. Bravo ; M. López-Hoyos ; J. Irure-Ventura ; E. Valeriano-Lorenzo ; M.T. García-Unzueta ; P. Sánchez-Juan ; E. Rodríguez-Rodríguez ; (2024): Diagnostic Accuracy of Plasma p-tau217 for Detecting Pathological Cerebrospinal Fluid Changes in Cognitively Unimpaired Subjects Using the Lumipulse Platform. The Journal of Prevention of Alzheimer’s Disease (JPAD). http://dx.doi.org/10.14283/jpad.2024.152

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