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 ... -  《-》

Core blood biomarkers of Alzheimer's disease: A single-center real-world performance study.

The new criteria for Alzheimer's disease pave the way for the introduction of core blood biomarkers of Alzheimer's disease (BBAD) into clinical practice. However, this depends on the demonstration of sufficient accuracy and robustness of BBADs in the intended population. To assess the diagnostic performance of core BBADs in our memory clinic, comparing them with cerebrospinal fluid (CSF) analysis. Real-world cross-sectional observational study. Memory Clinic of Fondazione IRCCS "San Gerardo dei Tintori," Monza, Italy. n = 102 consecutive outpatients (mean age: 71.0 ± 7.6 years) with cognitive impairment undergoing routine lumbar puncture. CSF Aβ40, Aβ42, tTau, and pTau181 levels were measured. Plasma biomarkers were evaluated using Lumipulse® G600II. Logistic regression and Receiver Operating Characteristic (ROC) analysis were used to assess biomarker performance. The diagnosis of Alzheimer's disease was based on CSF Aβ42/40 ratio. Plasma pTau217 demonstrated the highest diagnostic accuracy (AUC=0.91), followed by pTau181 (AUC=0.88) and Aβ42/40 (AUC=0.83). In robustness analyses, only pTau217 and pTau181 performance remained consistent, while that of Aβ42/40 ratio declined with added random variability. pTau217 significantly outperformed other BBAD, with the exception of pTau181. pTau BBAD were significant predictors of baseline Mini-Mental State Examination scores. Plasma pTau217, measured with Lumipulse®, is a robust and reliable BBAD for detecting amyloid pathology in a memory clinic setting, offering a practical and less invasive alternative to traditional CSF testing.

Pozzi FE ，Conti E ，Remoli G ，dell'Orto N ，Andreoni S ，Da Re F ，Sala G ，Cuffaro L ，Ferrarese C ，Appollonio I ，Zoia CP ，Tremolizzo L ... -  《-》

Analysis of Cerebrospinal Fluid, Plasma β-Amyloid Biomarkers, and Cognition from a 2-Year Phase 2 Trial Evaluating Oral ALZ-801/Valiltramiprosate in APOE4 Carriers with Early Alzheimer's Disease Using Quantitative Systems Pharmacology Model.

Hey JA ，Yu JY ，Abushakra S ，Schaefer JF ，Power A ，Kesslak P ，Tolar M ... -  《-》

Predicting Longitudinal Cognitive Decline and Alzheimer's Conversion in Mild Cognitive Impairment Patients Based on Plasma Biomarkers.

Park MK ，Ahn J ，Kim YJ ，Lee JW ，Lee JC ，Hwang SJ ，Kim KC ... -  《Cells》