Validation of the AD-CSF-index in autopsy-confirmed Alzheimer's disease patients and healthy controls.

Abstract

The cerebrospinal fluid (CSF) biomarkers amyloid-β peptide of 42 amino acids (Aβ1-42), total tau-protein (T-tau), and tau phosphorylated at threonine 181 (P-tau181P) are used to diagnose Alzheimer's disease (AD). In order to increase diagnostic power, several biomarker combinations have been proposed. In that sense, a new CSF biomarker index was developed, the AD-CSF-index, which has been validated in clinically diagnosed AD patients using electrochemoluminescence based Meso Scale Discovery and single-analyte ELISA kits. This study validated the AD-CSF-index in neuropathologically diagnosed AD patients, using both single-analyte ELISA and multi-analyte Luminex assays. CSF of 51 neuropathologically diagnosed AD patients and of 95 controls was analyzed by commercially available single-analyte ELISA-kits (INNOTEST, Innogenetics) and by a Research Use Only version of the multi-analyte Luminex xMAP assay (INNO-BIA AlzBio3, Innogenetics). Subsequently the AD-CSF-indices were calculated. Both T-tau and P-tau181P AD-CSF-indices were significantly increased in AD patients when compared to controls (p < 0.001). The diagnostic power of the indices was calculated using ROC analyses, resulting in excellent sensitivity and specificity values that systematically exceeded the 80% threshold for discriminating autopsy-confirmed AD patients from controls, independent of the analytical platform. The power to discriminate between AD and non-AD dementias was not included in this study and should be validated in the future. In conclusion, this study validated the AD-CSF-index in autopsy-confirmed AD patients and has shown that its excellent diagnostic accuracy is independent of the analytical platform.

• Authors: Hanne Struyfs, José L Molinuevo, Jean-Jacques Martin, Peter Paul De Deyn, Sebastiaan Engelborghs
• Journal: Journal of Alzheimer's disease : JAD (J Alzheimers Dis) Vol. 41 Issue 3 Pg. 903-9 ( 2014) ISSN: 1875-8908 [Electronic] Netherlands
• PMID: 24705548 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• tau Proteins

Topics

• Adult
• Aged
• Aged, 80 and over
• Alzheimer Disease (cerebrospinal fluid, pathology)
• Amyloid beta-Peptides (cerebrospinal fluid)
• Autopsy (methods)
• Enzyme-Linked Immunosorbent Assay
• Female
• Humans
• Male
• Middle Aged
• Psychiatric Status Rating Scales
• ROC Curve
• Sensitivity and Specificity
• tau Proteins (cerebrospinal fluid)