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

We compared the clinical and analytical performance of Alzheimer's disease (AD) plasma biomarkers measured using the single-molecule array (Simoa) and Lumipulse platforms. We quantified the plasma levels of amyloid beta 42 (Aß42), Aß40, phosphorylated tau (Ptau181), and total tau biomarkers in 81 patients with mild cognitive impairment (MCI), 30 with AD, and 16 with non-AD dementia. We found a strong correlation between the Simoa and Lumipulse methods. Concerning the clinical diagnosis, Simoa Ptau181/Aß42 (AUC 0.739, 95% CI 0.592-0.887) and Lumipulse Aß42 and Ptau181/Aß42 (AUC 0.735, 95% CI 0.589-0.882 and AUC 0.733, 95% CI 0.567-0.900) had the highest discriminating power. However, their power was significantly lower than that of CSF Aß42/Aß40, as measured by Lumipulse (AUC 0.879, 95% CI 0.766-0.992). Simoa Ptau181 and Lumipulse Ptau181/Aß42 were the markers most consistent with the CSF Aß42/Aß40 status (AUC 0.801, 95% CI 0.712-0.890 vs. AUC 0.870, 95% CI 0.806-0.934, respectively) at the ≥2.127 and ≥0.084 cut-offs, respectively. The performance of the Simoa and Lumipulse plasma AD assays is weaker than that of CSF AD biomarkers. At present, the analysed AD plasma biomarkers may be useful for screening to reduce the number of lumbar punctures in the clinical setting.

Sex specific EEG signatures associated with cerebrospinal fluid biomarkers in mild cognitive impairment.

OBJECTIVE: The use of the electroencephalography (EEG) technique in Alzheimer's disease (AD) diagnosis is scarce due to a lack of validation of its neurophysiological information with current biomarkers. Therefore, our goal was to assess correlations between brain spectral power signatures and cerebrospinal fluid markers (CSF) such as amyloid-ß 42 load (Aß-42), total tau (t-tau), and phosphorylated tau (p-tau) in a mild cognitive impairment (MCI) population. Furthermore, given the AD sex-dependent vulnerability related to CSF biomarkers, we went a little forward looking for different electrophysiological correlations for males and females independently. METHODS: A data-driven approach was employed to determine bidimensional spectral power signatures (space-frequency) that correlated (Spearman) significantly with any of the three CSF markers in 27 patients with MCI in any of the two sex-dependent subsamples (i.e., 12 females and 15 males). RESULTS: Our main significant outcomes evidenced 1) a negative correlation of Aß-42 load with central-posterior theta power and a negative correlation of t-tau with widespread alpha power within the male subsample, and 2) a significant negative correlation between t-tau and widespread beta power in the female subgroup. CONCLUSIONS: There is a distinctive profile of correlations between resting-state electrophysiological signatures and CSF markers in male and female individuals. SIGNIFICANCE: The combination of these two measures would be pointing out the need of a more personalized approach to promote early AD diagnosis.

Assessment of the Concordance and Diagnostic Accuracy Between Elecsys and Lumipulse Fully Automated Platforms and Innotest.

Manual ELISA assays are the most commonly used methods for quantification of biomarkers; however, they often show inter- and intra-laboratory variability that limits their wide use. Here, we compared the Innotest ELISA method with two fully automated platforms (Lumipulse and Elecsys) to determine whether these new methods can provide effective substitutes for ELISA assays. We included 149 patients with AD (n = 34), MCI (n = 94) and non-AD dementias (n = 21). Aß42, T-tau, and P-tau were quantified using the ELISA method (Innotest, Fujirebio Europe), CLEIA method on a Lumipulse G600II (Fujirebio Diagnostics), and ECLIA method on a Cobas e 601 (Roche Diagnostics) instrument. We found a high correlation between the three methods, although there were systematic differences between biomarker values measured by each method. Both Lumipulse and Elecsys methods were highly concordant with clinical diagnoses, and the combination of Lumipulse Aß42 and P-tau had the highest discriminating power (AUC 0.915, 95% CI 0.822-1.000). We also assessed the agreement of AT(N) classification for each method with AD diagnosis. Although differences were not significant, the use of Aß42/Aß40 ratio instead of Aß42 alone in AT(N) classification enhanced the diagnostic accuracy (AUC 0.798, 95% CI 0.649-0.947 vs. AUC 0.778, 95% CI 0.617-0.939). We determined the cut-offs for the Lumipulse and Elecsys assays based on the Aß42/Aß40 ratio ± status as a marker of amyloid pathology, and these cut-offs were consistent with those recommended by manufacturers, which had been determined based on visual amyloid PET imaging or diagnostic accuracy. Finally, the biomarker ratios (P-tau/Aß42 and T-tau/Aß42) were more consistent with the Aß42/Aß40 ratio for both Lumipulse and Elecsys methods, and Elecsys P-tau/Aß42 had the highest consistency with amyloid pathology (AUC 0.994, 95% CI 0.986-1.000 and OPA 96.4%) at the ≥0.024 cut-off. The Lumipulse and Elecsys cerebrospinal fluid (CSF) AD assays showed high analytical and clinical performances. As both automated platforms were standardized for reference samples, their use is recommended for the measurement of CSF AD biomarkers compared with unstandardized manual methods, such as Innotest ELISA, that have demonstrated a high inter and intra-laboratory variability.