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Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease

Overview of attention for article published in Alzheimer's Research & Therapy, February 2018
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Title
Characterization and clinical use of inflammatory cerebrospinal fluid protein markers in Alzheimer’s disease
Published in
Alzheimer's Research & Therapy, February 2018
DOI 10.1186/s13195-018-0353-3
Pubmed ID
Authors

Frederic Brosseron, Andreas Traschütz, Catherine N. Widmann, Markus P. Kummer, Pawel Tacik, Francesco Santarelli, Frank Jessen, Michael T. Heneka

Abstract

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. 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. 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. 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.

Twitter Demographics

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Mendeley readers

The data shown below were compiled from readership statistics for 125 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 125 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 25 20%
Student > Ph. D. Student 22 18%
Student > Master 15 12%
Student > Bachelor 10 8%
Other 7 6%
Other 18 14%
Unknown 28 22%
Readers by discipline Count As %
Neuroscience 24 19%
Medicine and Dentistry 18 14%
Biochemistry, Genetics and Molecular Biology 16 13%
Agricultural and Biological Sciences 8 6%
Nursing and Health Professions 3 2%
Other 18 14%
Unknown 38 30%

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 27 February 2018.
All research outputs
#18,589,103
of 23,025,074 outputs
Outputs from Alzheimer's Research & Therapy
#1,177
of 1,244 outputs
Outputs of similar age
#256,746
of 330,211 outputs
Outputs of similar age from Alzheimer's Research & Therapy
#26
of 35 outputs
Altmetric has tracked 23,025,074 research outputs across all sources so far. This one is in the 11th percentile – i.e., 11% of other outputs scored the same or lower than it.
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