AUTHOR=Oudart Jean-Baptiste , Djerada Zoubir , Nonnonhou Vignon , Badr Sarah , Bertholon Laurie-Anne , Dammak Anis , Jaidi Yacine , Novella Jean-Luc , Pallet Nicolas , Gillery Philippe , Mahmoudi Rachid TITLE=Incremental Value of CSF Biomarkers in Clinically Diagnosed AD and Non-AD Dementia JOURNAL=Frontiers in Neurology VOLUME=11 YEAR=2020 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2020.00560 DOI=10.3389/fneur.2020.00560 ISSN=1664-2295 ABSTRACT=

Background: Cerebrospinal fluid (CSF) biomarkers are used to diagnose Alzheimer disease (AD), especially in atypical clinical presentations. No consensus currently exists regarding cut-off values. This study aimed, firstly, to define optimal cut-off values for CSF biomarkers, and secondly, to investigate the most relevant diagnostic strategy for AD based on CSF biomarker combinations.

Methods: A total of 380 patients were prospectively included: 140 with AD, 240 with various neurological diagnoses (non-AD). CSF biomarkers were measured using ELISA. Univariate and multivariate analyses were performed using random forest and logistic regression approaches.

Results: Univariate receiver operating curve curves analysis of T-Tau, P-Tau₁₈₁, Aβ₄₂, Aβ₄₀ concentrations, and Aβ₄₂/Aβ₄₀ ratio levels showed AD cut-off values of ≥355, ≥57, ≤706, ≥10,854, and ≤0.059 ng/L, respectively. Multivariate analysis using random forest and logistic regression found that the algorithm based on P-Tau₁₈₁, Aβ₄₂ concentrations and Aβ₄₂/Aβ₄₀ ratio yielded the best discrimination between AD and non-AD populations. The cross-validation technique of the final model showed a mean accuracy of 0.85 and a mean AUC of 0.89.

Conclusion: This study confirms that the Aβ₄₂/Aβ₄₀ ratio was more useful than the Aβ₄₀ concentration in discriminating AD from non-AD populations in daily practice. These results indicate that the Aβ₄₂/Aβ₄₀ ratio should be assessed in all cases, independently of Aβ₄₂ concentrations.