Additional Use of Aβ 42 /Aβ 40 Ratio with Cerebrospinal Fluid Biomarkers P-Tau and Aβ 42 Increases the Level of Evidence of Alzheimer's Disease Pathophysiological Process in Routine Practice

Abstract

Background:

Cerebrospinal fluid (CSF) biomarkers have recently been included in the criteria for the diagnosis of Alzheimer’s disease (AD). Since interpretation of CSF profile requires the combination of three parameters, biological data are not always conclusive and isolated elevation of phosphorylated tau (P-tau) or reduction of amyloid-β (Aβ)₄₂ alone can be observed. In these cases, Aβ₄₂/Aβ₄₀ ratio could be more relevant than Aβ₄₂ absolute values by considering inter-individual variations in the total amyloid load.

Objective:

The objective of this study was to assess the use of Aβ₄₂/Aβ₄₀ ratio to improve the accuracy of biological conclusions in the diagnosis of patients with ambiguous CSF Aβ₄₂ or tau results.

Methods:

Among 386 lumbar punctures analyzed in the lab in 2 years, 122 showed ambiguous biological data that were completed by CSF Aβ₄₀ quantification and Aβ₄₂/Aβ₄₀ ratio calculation. A biological conclusion was then made using 0.05 as the Aβ₄₂/Aβ₄₀ ratio cut-off.

Results:

Our results showed that one-third of the biological profiles of patients with atypical dementia were ambiguous. The addition of Aβ₄₂/Aβ₄₀ ratio increased the proportion of interpretable biological profiles from 69% to 87%, without changing the conclusion when usual biomarkers (Aβ₄₂ and P-tau) were concordant.

Conclusion:

Our results support the use of the Aβ₄₂/Aβ₄₀ ratio in addition to the usual CSF AD biomarkers for patients with ambiguous biological profiles. This method could be specifically directed to this population in order to improve the level of certainty for clinical routine practice.