Improved Differential Diagnosis of Alzheimers Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers

← Back to publications

Published: 2019-01-08

Formatted citation

Khoonsari PE, Shevchenko G, Herman S, Remnestål J, Giedraitis V, Brundin R, Degerman Gunnarsson M, Kilander L, Zetterberg H, Nilsson P, Lannfelt L, Ingelsson M, Kultima K.. Improved Differential Diagnosis of Alzheimers Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid Biomarkers.
J Alzheimers Dis. (2019). DOI: 10.3233/JAD-180855

Abstract

BACKGROUND: Alzheimers disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: Aβ42, total tau (t-tau), and phosphorylated tau (p-tau) in cerebrospinal fluid (CSF). Although the sensitivities and specificities of the classical biomarkers are fairly good for detection of AD, there is still a need to develop novel biochemical markers for early detection of AD. OBJECTIVE: We explored if integration of novel proteins with classical biomarkers in CSF can better discriminate AD from non-AD subjects. METHODS: We applied ELISA, mass spectrometry, and multivariate modeling to investigate classical biomarkers and the CSF proteome in subjects (nu200a=u200a206) with 76 AD patients, 74 mild cognitive impairment (MCI) patients, 11 frontotemporal dementia (FTD) patients, and 45 non-dementia controls. The MCI patients were followed for 4-9 years and 21 of these converted to AD, whereas 53 remained stable. RESULTS: By combining classical CSF biomarkers with twelve novel markers, the area of the ROC curves (AUROCS) of distinguishing AD and MCI/AD converters from non-AD were 93% and 96%, respectively. The FTDs and non-dementia controls were identified versus all other groups with AUROCS of 96% and 87%, respectively. CONCLUSIONS: Integration of new and classical CSF biomarkers in a model-based approach can improve the identification of AD, FTD, and non-dementia control subjects.