Diagnostic performance of cerebrospinal fluid biomarkers and their ratios in Alzheimer's disease

Details

Supervisors

Ivanoiu, Adrian

Faculty

Faculté de médecine et médecine dentaire

Degree label

Master [180] en médecine

Abstract

Background: The classical amyloid-β (Aβ), and tau cerebrospinal fluid (CSF) biomarkers are now widely used for the diagnosis of Alzheimer’s disease (AD). Aβ40 is the most abundant Aβ peptide isoform in the CSF, and the Aβ42/Aβ40 concentration ratio has been proposed to better reflect the brain amyloid burden than the CSF Aβ42 concentration alone. Objective: The main objective of this retrospective study is to evaluate the contribution of the classical CSF biomarkers, as well as the Aβ42/Aβ40 ratio, to the accuracy of the AD diagnosis. Methods: 148 patients diagnosed with AD, mild cognitive impairment (MCI), other non degenerative neurological conditions and healthy controls were included. A total of 112 CSF samples were quantified by the INNOTEST or Lumipulse immunoassays. Statistical analysis was performed to assess the biomarker differences in the respective patient subgroups and the diagnostic performance of the biomarkers was compared using external and internal cutoff values. Results: For the discrimination between control and AD subjects, the Aβ42/Aβ40 ratio had the highest area under the receiver operating characteristic (ROC) curve (AUC: 0.93 [0.85 – 0.93], sensitivity: 0.96, specificity: 0.84), followed by the t tau/Aβ42 ratio (AUC: 0.91 [0.80 – 1], sensitivity: 0.96, specificity: 0.84), but the difference was not statistically significant in this study’s cohort of patients. The biomarker ratios performed better than the single biomarkers (AUC: 0.80 [0.67 – 0.94], sensitivity: 0.87, specificity: 0.76 for Aβ42; AUC: 0.89 [0.80 – 0.99], sensitivity: 0.83, specificity: 0.92 for t-tau). For the distinction between Non AD and AD subjects, the Aβ42/Aβ40 ratio outperformed the CSF Aβ42 alone, but was not significantly better than the other markers (AUC: 0.84 [0.75 – 0.94] sensitivity: 0.91, specificity: 0.73; AUC: 0.53 [0.39 – 0.68], sensitivity: 0.91, specificity 0.27; AUC: 0.78 [0.67 – 0.90], sensitivity 0.83, specificity: 0.66; AUC: 0.76 [0.64 – 0.89], sensitivity: 0.83, specificity: 0.67 for Aβ42/Aβ40, Aβ42, t-tau and t-tau/Aβ42 ratio respectively). Conclusion: The results of this study indicate an advantage of using the CSF Aβ42/Aβ40 concentration ratio compared to the classical markers in some clinical settings.