Search

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-Tau 181 , Aβ 42 , Aβ 40 concentrations, and Aβ 42 /Aβ 40 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-Tau 181 , Aβ 42 concentrations and Aβ 42 /Aβ 40 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 Aβ 42 /Aβ 40 ratio was more useful than the Aβ 40 concentration in discriminating AD from non-AD populations in daily practice. These results indicate that the Aβ 42 /Aβ 40 ratio should be assessed in all cases, independently of Aβ 42 concentrations., (Copyright © 2020 Oudart, Djerada, Nonnonhou, Badr, Bertholon, Dammak, Jaidi, Novella, Pallet, Gillery and Mahmoudi.)

Background Identifying frail elderly subjects is of paramount importance in order to conduct a tailored care. The characterization of frailty status is currently based on the collection of clinical data and on the use of various tools such as Fried's criteria, which constitutes a difficult and time-consuming process. Up to now, no biological markers have been described as reliable tools for frailty characterization. We tested the hypothesis that a link between frailty and protein molecular aging existed. This study aimed therefore at determining whether post-translational modification derived products (PTMDPs), recognized as biomarkers of protein aging, were associated with frailty status in elderly subjects. Methods Frailty status was determined according to Fried's criteria in 250 elderly patients (>65 years old) hospitalized in a short-term care unit. Serum concentrations of protein-bound PTMDPs, including carboxymethyllysine (CML), pentosidine, methylglyoxal-hydroimidazolone-1 and homocitrulline (HCit), were determined by liquid chromatography coupled with tandem mass spectrometry, and tissue content of advanced glycation end-products was assessed by skin autofluorescence (SAF) measurement. Associations between PTMDPs and frailty status were analyzed using logistic regression models. Results Frail patients had significantly (p<0.01) higher CML, HCit, and SAF values compared to non-frail and pre-frail subjects. By multivariate analysis, only HCit concentrations and SAF values remained associated with frailty status (p=0.016 and p=0.002, respectively), independently of age, comorbidities, renal function, C-reactive protein and albumin concentrations. Conclusions HCit and SAF are significantly associated with frailty status in elderly subjects. This study suggests that PTMDPs constitute promising biomarkers for identifying frail patients and guiding personalized patient care.