The CORCOBIA study: Cut-off points of Alzheimer's disease CSF biomarkers in a clinical cohort

Introduction: The analysis of the core biomarkers of Alzheimer's Disease (AD) in the cerebrospinal fluid (CSF) is recommended in the clinical units where it is available. Because of the absence of universal validated values, the determination of specific cut-off points for each center and its population is recommended. The main objective of the CORCOBIA study was to determine the cut-off points of core AD CSF biomarkers for several centers (Parc de Salut Mar, Barcelona and Hospital General de Granollers), which work with the same reference laboratory (Laboratori de Referència de Catalunya).

Methods: Prospective study including cognitively healthy subjects (HC, n = 42), subjects with amnestic mild cognitive impairment (aMCI, n = 35) and patients with dementia due to Alzheimer's Disease (AD, n = 48), in whom clinical and neuropsychological assessment, neuroimaging, APOE genotyping and lumbar puncture to analyze amyloid beta peptides (Aβ42, Aβ40), total tau (tTau) and phosphorylated Tau (pTau181) using the Lumipulse G600II (Fujirebio) was performed. The values of Sensitivity (Se), Specificity (Sp), predictive values and area under the curve (AUC) were calculated, determining the cut-off point according to the Youden index by comparing the groups of HC and AD.

Results: The resulting cut-offs and their AUC were the following: Aβ42 750 pg/ml (AUC 0.809); Aβ42/Aβ40 0.062 (AUC 0.78); pTau181 69.85 pg/ml (AUC 0.81); tTau 522.0 pg/ml (AUC 0.79); Aβ42/tTau 1.76 (AUC 0.86); Aβ42/pTau181 10.25 (AUC 0.86).

Conclusions: The determination of cut-off points of core AD CSF biomarkers for the participating centers allows a better diagnostic accuracy. The ratio CSF Aβ42/pTau181 shows the highest AUC and better balance between sensitivity and specificity.