Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid-binding protein 3 and ferritin to neurodegeneration and neuroinflammation.
[en] There is growing evidence that promising biomarkers of inflammation in Alzheimer´s disease (AD) and other neurodegenerative diseases correlate strongest to levels of tau or neurofilament, indicating an inflammatory response to neuronal damage or death. To test this hypothesis, we investigated three AD candidate markers (ferritin, fatty acid binding protein 3 (FABP-3), and neurogranin) in interrelation to established AD and inflammatory protein markers. We further aimed to determine if such interrelations would be evident in pathological subjects only or also under non-pathological circumstances. Cerebrospinal fluid levels of the three proteins were quantified in samples from the University Clinic of Bonn (UKB) Department of Neurodegenerative Diseases & Geriatric Psychiatry, Germany. Data were analyzed based on clinical or biomarker-defined stratification of subjects with adjustment for covariates age, sex, and APOE status. Levels of ferritin, FABP-3 and neurogranin were elevated in subjects with pathological levels of t-tau independent of beta-amyloid status. The three markers correlated with each other, tau isoforms, age, and those inflammatory markers previously described as related to neurodegeneration, predominantly sTREM2, macrophage migration inhibitory factor, soluble vascular endothelial growth factor receptor, soluble vascular cell adhesion molecule 1 (sVCAM-1), and C1q. These interrelations existed in subjects with pathological and sub-pathological tau levels, in particular for FABP-3 and neurogranin. Relations to ferritin were independent of absolute levels of tau, too, but showed differing trajectories between pathological and non-pathological subjects. A specific set of inflammatory markers is highly related to markers of neuronal damage such as tau, neurogranin, or FABP-3. These proteins could be used as readouts of the inflammatory response during the neurodegeneration phase of AD.
Disciplines :
Neurology
Author, co-author :
Brosseron, Frederic; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany
Kleemann, Kilian; University of Glasgow, Glasgow, UK
Kolbe, Carl-Christian; Institute of Innate Immune, University of Bonn Medical Center, Bonn, Germany
Santarelli, Francesco; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany
Castro-Gomez, Sergio ; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany
Tacik, Pawel; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany
Latz, Eicke; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Institute of Innate Immune, University of Bonn Medical Center, Bonn, Germany
Jessen, Frank; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Psychiatry, Medical Faculty, University of Cologne, Cologne, Germany
HENEKA, Michael ; German Center for Neurodegenerative Diseases (DZNE), Bonn, Germany ; Department of Neurodegenerative Diseases & Geropsychiatry/Neurology, University of Bonn Medical Center, Bonn, Germany
External co-authors :
yes
Language :
English
Title :
Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid-binding protein 3 and ferritin to neurodegeneration and neuroinflammation.
Deutsche Forschungsgemeinschaft Deutsches Zentrum für Neurodegenerative Erkrankungen Helmholtz-Gemeinschaft Deutsche Forschungsgemeinschaft
Funding text :
This work was funded by the German Center for Neurodegenerative Diseases (DZNE e.V.) within the Helmholtz Association and by the German Research Council (DFG, Deutsche Forschungsgemeinschaft KFO177, TP4). FB, CCK, EL and MTH are members of the Cluster of Excellence “Immunosensation.”
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