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

• Published in: Fluids and barriers of the CNS Vol. 22; no. 1; pp. 9 - 11
• Main Authors: Catania, Marcella, Battipaglia, Claudia, Perego, Alberto, Salvi, Erika, Maderna, Emanuela, Cazzaniga, Federico Angelo, Rossini, Paolo M., Marra, Camillo, Vanacore, Nicola, Redolfi, Alberto, Perani, Daniela, Spadin, Patrizia, Cotelli, Maria, Cappa, Stefano, Caraglia, Naike, Tiraboschi, Pietro, Tagliavini, Fabrizio, Di Fede, Giuseppe
• Format: Journal Article
• Language: English
• Published: London BioMed Central 21.01.2025; BioMed Central Ltd; BMC
• Subjects: Advertising executives; Aged; Aged, 80 and over; Alzheimer Disease - blood; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - blood; Amyloid beta-Peptides - cerebrospinal fluid; Automation; Biomarkers; Biomarkers - blood; Biomarkers - cerebrospinal fluid; Biomedical and Life Sciences; Biomedicine; Cerebrospinal fluid; Chemiluminescence; Clinical medicine; Cognitive ability; Cognitive Dysfunction - blood; Cognitive Dysfunction - cerebrospinal fluid; Cognitive Dysfunction - diagnosis; CSF; Dementia; Development and progression; Diagnosis; Diagnostic tests; Drug approval; Enzyme immunoassay; Enzymes; Ethylenediaminetetraacetic acid; Female; Hematology; Humans; Immunoassay; Male; Measuring instruments; Middle Aged; Mild Cognitive Impairment; Neurobiology; Neurodegenerative diseases; Neuropathology; Neuropsychology; Neurosciences; Peptide Fragments - blood; Peptide Fragments - cerebrospinal fluid; Plasma; Plasma levels; Statistical analysis; tau Proteins - blood; tau Proteins - cerebrospinal fluid; β-Amyloid; Italy; Taiwan; Plasma; Aβ; Alzheimer’s disease; CSF; Biomarkers; Diagnosis; Lumipulse; Mild Cognitive Impairment; pTau
• ISSN: 2045-8118; 2045-8118
• DOI: 10.1186/s12987-025-00620-5

Background 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). Methods 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. Results 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. Conclusions Our results suggest that plasma biomarkers, and especially Aβ42/Aβ40 ratio and pTau217, are promising candidates for the early detection of AD pathology.