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

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). Prospective study including cognitively unimpaired individuals (CU, 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 analyse 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 CU and AD groups. 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). 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.

Puig-Pijoan A ，García-Escobar G ，Fernández-Lebrero A ，Manero-Borràs RM ，Sánchez-Benavides G ，Navalpotro-Gómez I ，Cascales Lahoz D ，Suárez-Calvet M ，Grau-Rivera O ，Boltes Alandí A ，Pont-Sunyer MC ，Ortiz-Gil J ，Carrillo-Molina S ，López-Villegas D ，Abellán-Vidal MT ，Martínez-Casamitjana MI ，Hernández-Sánchez JJ ，Peña-Casanova J ，Roquer J ，Padrós Fluvià A ，Puente-Périz V ... -  《-》

Elecsys Cerebrospinal Fluid Assays Accurately Distinguish Alzheimer's Disease from Frontotemporal Lobar Degeneration.

Ortner M ，Goldhardt O ，Diehl-Schmid J ，Yakushev I ，Lanz K ，Hedderich DM ，Manuilova E ，Simon M ，Weinberger JP ，Grimmer T ... -  《-》

Assessment of the Correlation and Diagnostic Accuracy between Cerebrospinal Fluid and Plasma Alzheimer's Disease Biomarkers: A Comparison of the Lumipulse and Simoa Platforms.

Dakterzada F ，Cipriani R ，López-Ortega R ，Arias A ，Riba-Llena I ，Ruiz-Julián M ，Huerto R ，Tahan N ，Matute C ，Capetillo-Zarate E ，Piñol-Ripoll G ... -  《-》

Exploring the ability of plasma pTau217, pTau181 and beta-amyloid in mirroring cerebrospinal fluid biomarker profile of Mild Cognitive Impairment by the fully automated Lumipulse(®) platform.

The approval of new disease-modifying therapies by the U.S. Food and Drug Administration and the European Medicine Agency makes it necessary to optimize non-invasive and cost-effective tools for the identification of subjects at-risk of developing Alzheimer's Disease (AD). Plasma biomarkers are excellent candidates. However, their ability to reflect the cerebrospinal fluid (CSF) profile - that remains to date the gold standard for the biochemical diagnosis of AD - needs to be confirmed and validated before their implementation in clinical practice. The aims of this study are to analyse the correlation between CSF and plasma Aβ40, Aβ42, Aβ42/Aβ40 and pTau181, and to assess the diagnostic performance of plasma biomarkers in a cohort of subjects affected by Mild Cognitive Impairment (MCI). The study was performed on 306 subjects affected by MCI, enrolled in the context of the Italian Interceptor Project. Aβ40, Aβ42 and pTau181 were analysed in plasma and CSF, and pTau217 was measured in plasma. The fully automated chemiluminescence enzyme immunoassay and the Lumipulse® G600II (Fujirebio) instrument were used for all measurements. We analysed the correlations between CSF and plasma biomarkers and the differences of plasma biomarker concentrations after grouping MCI cases according to AT classification of CSF AD biomarker profiles. We found statistically significant positive correlations between CSF and plasma Aβ42, Aβ42/Aβ40 ratio and pTau181. All the biomarkers, except Aβ40, showed differences in A+ vs. A-, A+T+ vs. A-T- and A+T- vs. A-T- patients. Moreover, Aβ42 and Aβ42/Aβ40 plasma levels were lower in A+T- compared to A-T- and A-T+ groups, and pTau181 and pTau217 plasma levels were higher in A+T+ compared to A+T-. Aβ42/Aβ40 and pTau217 showed a robust performance in distinguishing A+ from A- (AUC = 0.857 and 0.862, respectively) and A+T+ from A-T- (AUC = 0.866 and 0.911) subjects. Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.

Catania M ，Battipaglia C ，Perego A ，Salvi E ，Maderna E ，Cazzaniga FA ，Rossini PM ，Marra C ，Vanacore N ，Redolfi A ，Perani D ，Spadin P ，Cotelli M ，Cappa S ，Caraglia N ，Tiraboschi P ，Tagliavini F ，Di Fede G ... -  《Fluids and Barriers of the CNS》

Real-life reliability of plasma pTau181, Aβ(42)/Aβ(40), and pTau181/Aβ(42) measured by Lumipulse G600II in predicting cerebrospinal fluid amyloid status.

Imperiale D ，Atzori C ，Angeloro DP ，Murgioni A ，Bagatin A ，Secci V ，Calcagno A ，Capobianco M ，Coletti Moja M ，Rota E ，Bongioanni MR ，Rosso M ，Godi L ，Barra M ，De Mattei M ，Bonzanino M ，Ferrandi D ，Rainero I ，Lopiano L ，Bozzali M ... -  《-》