The AD-CSF-index discriminates Alzheimer's disease patients from healthy controls: a validation study

AD-CSF 指数区分阿尔茨海默病患者与健康对照者:一项验证研究

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作者:Jose L Molinuevo, Juan Domingo Gispert, Bruno Dubois, Michael T Heneka, Alberto Lleo, Sebastiaan Engelborghs, Jesús Pujol, Leonardo Cruz de Souza, Daniel Alcolea, Frank Jessen, Marie Sarazin, Foudil Lamari, Mircea Balasa, Anna Antonell, Lorena Rami

Background

Cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) show an acceptable diagnostic sensitivity and specificity; however, their interpretation and ease of use is far from optimal.

Conclusion

The AD-CSF-index represents a novel approach, combining normalized CSF values, for the biological diagnosis of AD. The AD-CSF-index presents an optimal AUC with high sensitivity and specificity and seems to be a simple and intuitive way to interpret AD CSF biomarker results even from different analytical platforms.

Methods

A total of 342 subjects, 103 healthy controls and 239 AD patients, from four European memory clinics were included. The AD-CSF-index was constructed from the addition of normalized values between the minimum and maximum of amyloid and tau protein levels. The diagnostic accuracy, receiver operating characteristic, and regression analysis of the AD-CSF-index and other composite indices were evaluated in this study.

Objective

To study and validate the diagnostic accuracy of an easy-to-use normalized CSF biomarker index, the AD-CSF-index, in different European populations.

Results

AD patients presented a significantly higher AD-CSF-index than healthy subjects (control = 0.5204; AD = 1.2272; p < 0.001). The AD-CSF-index obtained a sensitivity of 88.6% at 85% specificity and also showed a significantly higher diagnostic power (p < 0.05) than the individual CSF biomarkers and other studied indices. The performance of the AD-CSF-index was very similar between ELISA and MesoScale measurements. Cut-off values of approximately 0.75 provided the lowest achievable overall classification errors and a cut-off point of about 0.95 consistently provided specificities above 85%.

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