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.
Highlights
Alzheimer disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease clinically characterized by memory impairment and/or deficit in other cognitive domains associated with functional decline [1]
T-Tau and P-Tau181 concentrations were significantly higher in the AD population than in the non-AD population (617 and 82 ng/L vs. 319 and 47 ng/L, p < 0.001, respectively) whereas cerebrospinal fluid (CSF) Aβ42 concentration and Aβ42/Aβ40 ratio were significantly lower in AD vs. nonAD patients (513 ng/L and 0.044 vs. 786 ng/L and 0.077, p < 0.001, respectively)
Univariate receiver operating characteristics (ROC) curves analyses of T-Tau, P-Tau181, Aβ42, Aβ40 concentrations and Aβ42/Aβ40 ratio levels yielded cut-off values for the diagnosis of AD of ≥355, ≥57, ≤706, ≥10,854, and ≤0.059 ng/L, respectively (Figure 1)
Summary
Alzheimer disease (AD), the most common cause of dementia, is a progressive neurodegenerative disease clinically characterized by memory impairment and/or deficit in other cognitive domains associated with functional decline [1]. The diagnosis of AD remained probabilistic and was based on clinical features associated with neuropsychological testing and neuroimaging [2]. These old criteria were useful at the stage of dementia and were defined as cognitive impairment including memory impairment impeding daily life activities and interactions with the social network. This clinical diagnostic method led to a diagnosis of “probable” and “possible” AD, based on different levels of clinical confidence. 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
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