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

Artikel i vetenskaplig tidskrift
Författare P. E. Khoonsari
G. Shevchenko
S. Herman
J. Remnestal
V. Giedraitis
R. Brundin
M. D. Gunnarsson
L. Kilander
Henrik Zetterberg
P. Nilsson
L. Lannfelt
M. Ingelsson
K. Kultima
Publicerad i Journal of Alzheimers Disease
Volym 67
Nummer/häfte 2
Sidor 639-651
ISSN 1387-2877
Publiceringsår 2019
Publicerad vid Institutionen för neurovetenskap och fysiologi, sektionen för psykiatri och neurokemi
Sidor 639-651
Språk en
Länkar dx.doi.org/10.3233/jad-180855
Ämnesord Alzheimer's disease, cerebrospinal fluid, ELISA, mass spectrometry, mild cognitive impairment, mild cognitive impairment, apolipoprotein-a-i, clinical-diagnosis, csf, biomarkers, protein, identification, neurogranin, proteomics, consensus, workflow
Ämneskategorier Neurologi

Sammanfattning

Background: Alzheimer's disease (AD) is diagnosed based on a clinical evaluation as well as analyses of classical biomarkers: A beta(42), 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 (n = 206) 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 MCl/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.

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