Improved Differential Diagnosis of Alzheimer's Disease by Integrating ELISA and Mass Spectrometry-Based Cerebrospinal Fluid BiomarkersShow others and affiliations
2019 (English)In: Journal of Alzheimer's Disease, ISSN 1387-2877, E-ISSN 1875-8908, Vol. 67, no 2, p. 639-651Article in journal (Refereed) Published
Abstract [en]
Background: Alzheimer’s 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 (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 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.
Place, publisher, year, edition, pages
IOS PRESS , 2019. Vol. 67, no 2, p. 639-651
Keywords [en]
Alzheimer's disease, cerebrospinal fluid, ELISA, mass spectrometry, mild cognitive impairment, proteomics
National Category
Neurology Geriatrics
Identifiers
URN: urn:nbn:se:uu:diva-377711DOI: 10.3233/JAD-180855ISI: 000457779300016PubMedID: 30614806OAI: oai:DiVA.org:uu-377711DiVA, id: diva2:1294682
Funder
VINNOVAGun och Bertil Stohnes StiftelseÅke Wiberg FoundationStiftelsen Gamla Tjänarinnor2019-03-082019-03-082019-04-29Bibliographically approved