Universität zu Köln

Brosseron, Frederic, Traschuetz, Andreas, Widmann, Catherine N., Kummer, Markus P., Tacik, Pawel, Santarelli, Francesco, Jessen, Frank and Heneka, Michael T. (2018). Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer's disease. Alzheimers Res. Ther., 10. LONDON: BIOMED CENTRAL LTD. ISSN 1758-9193

Full text not available from this repository.

Abstract

Background: Neuroinflammation has gained increasing attention as a potential contributing factor in Alzheimer's disease (AD) pathology. A clinical cerebrospinal fluid biomarker capable of monitoring this process during the course of the disease has yet to emerge, chiefly owing to contradictory research findings. In this study, we sought to clarify the utility of inflammatory biomarkers in diagnostic procedures of AD in three steps: (1) to screen for proteins that are robustly detectable in cerebrospinal fluid; (2) based on this analysis, to explore any associations between the analytically robust markers and salient pathological features of AD; and (3) to determine the discriminative power of these markers in the clinical diagnosis of AD. Methods: From a total of 46 proteins, 15 that were robustly detectable in cerebrospinal fluid were identified. A subsequent analysis of these markers in a cohort of 399 patients (nondemented subjects, patients with mild cognitive impairment [MCI], and patients with AD, supplemented by smaller cohorts of other diseases) was conducted. Fluid biomarker data were related to AD pathology and neuropsychological markers and adjusted for confounders such as age, sex, apolipoprotein E genotype, and biobank storage time. Results: Cerebrospinal fluid levels of C-reactive protein and soluble TREM2 differed between nondemented subjects, patients with MCI, or patients with AD and were associated with amyloid and tau pathology. Several markers were associated with tau pathology only or with other neurodegenerative diseases. Correlations between neuropsychological performance and inflammatory markers were weak, but they were most prominent in AD and for the most challenging cognitive tests. All investigated covariates had significant influence, with varying effects across the markers. Still, none of the markers achieved discriminative power of more than 70% to distinguish between patient groups defined by clinical or neuropathological categories. Conclusions: Basic analytical considerations proved indispensable for this type of study because only one-third of the tested markers were robustly detectable in cerebrospinal fluid. Detectable inflammatory protein markers were associated in multiple ways with AD pathology. Yet, even significantly associated markers were not powerful enough in terms of effect strength, sensitivity, and specificity, and hence they were not suited for direct use in clinical diagnostic practice. Targets other than those most commonly considered in this field of research might provide results with better clinical applicability.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Brosseron, Frederic UNSPECIFIED UNSPECIFIED UNSPECIFIED Traschuetz, Andreas UNSPECIFIED UNSPECIFIED UNSPECIFIED Widmann, Catherine N. UNSPECIFIED UNSPECIFIED UNSPECIFIED Kummer, Markus P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Tacik, Pawel UNSPECIFIED UNSPECIFIED UNSPECIFIED Santarelli, Francesco UNSPECIFIED UNSPECIFIED UNSPECIFIED Jessen, Frank UNSPECIFIED UNSPECIFIED UNSPECIFIED Heneka, Michael T. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-195550
DOI:	10.1186/s13195-018-0353-3
Journal or Publication Title:	Alzheimers Res. Ther.
Volume:	10
Date:	2018
Publisher:	BIOMED CENTRAL LTD
Place of Publication:	LONDON
ISSN:	1758-9193
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language C-REACTIVE PROTEIN; NEURONAL INJURY; SOLUBLE TREM2; METAANALYSIS; ASSOCIATION; RISK; BIOMARKERS; MICROGLIA; CYTOKINES; DEMENTIA Multiple languages Clinical Neurology; Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/19555