Interrelations of Alzheimer´s disease candidate biomarkers neurogranin, fatty acid‐binding protein 3 and ferritin to neurodegeneration and neuroinflammation

Autor: Frank Jessen, Carl-Christian Kolbe, Sergio Castro-Gomez, Pawel Tacik, Kilian Kleemann, Eicke Latz, Francesco Santarelli, Frederic Brosseron, Michael T. Heneka
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Apolipoprotein E
Alzheimer´s disease
Biochemistry
neuroinflammation
Cohort Studies
pathology [Alzheimer Disease]
0302 clinical medicine
cerebrospinal fluid [Ferritins]
Neurogranin
biology
Neurodegeneration
pathology [Neurodegenerative Diseases]
neurodegeneration
Neurodegenerative Diseases
cerebrospinal fluid [Alzheimer Disease]
cerebrospinal fluid [Inflammation]
cerebrospinal fluid [Biomarkers]
biomarker
Biomarker (medicine)
Female
medicine.symptom
Fatty Acid Binding Protein 3
medicine.medical_specialty
Inflammation
03 medical and health sciences
Cellular and Molecular Neuroscience
Alzheimer Disease
Internal medicine
medicine
Humans
ddc:610
Neuroinflammation
pathology [Inflammation]
business.industry
medicine.disease
Ferritin
030104 developmental biology
Endocrinology
Ferritins
biology.protein
cerebrospinal fluid [Neurodegenerative Diseases]
Macrophage migration inhibitory factor
cerebrospinal fluid [Neurogranin]
business
Biomarkers
030217 neurology & neurosurgery
cerebrospinal fluid [Fatty Acid Binding Protein 3]
Zdroj: Journal of neurochemistry 157(6), 2210-2224 (2021). doi:10.1111/jnc.15175
ISSN: 1471-4159
0022-3042
DOI: 10.1111/jnc.15175
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: