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

Abstract

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.

Association of Endogenous Erythropoietin Levels and Iron Status With Cognitive Functioning in the General Population

“…In the patient setting of neurodegenerative diseases, strong associations of cerebrospinal fluid ferritin have been identified with worse cognitive function in patients with Alzheimer's disease, patients with Parkinson's disease, and patients with dementia with Lewy bodies (Ayton et al, 2022). In fact, cerebrospinal fluid ferritin levels even predicted outcomes in patients with Alzheimer's disease (Ayton et al, 2015(Ayton et al, , 2017, and could be used as a readout for the inflammatory response during the neurodegenerative phase of Alzheimer's disease (Brosseron et al, 2021).…”

Synthesis and Bioactivity Evaluation of a Novel 1,2,4-Oxadiazole Derivative in vitro and in 3×Tg Mice

“…The Fabp3 was a lipid metabolism-related biomarker of AD 35 and was positively correlated with inflammation and activation of astrocytes of AD patients. 36 , 37 The increased expression of Fabp3 in AD mice marked its dysfunction of lipid metabolism and immune state. The wyc-7-20 treatment reversed the increased expression of Cyp2e1 and Fabp3 ( Figure 5A and B , p < 0.05), suggesting that wyc-7-20 could improve the lipid metabolism and reduction of ROS in AD mice.…”

Temporal Cortex Microarray Analysis Revealed Impaired Ribosomal Biogenesis and Hyperactivity of the Glutamatergic System: An Early Signature of Asymptomatic Alzheimer's Disease

“…The altered expression of NRGN leads to loss of synaptic plasticity and schizophrenia-associated cognitive deficits (Hwang et al, 2021 ). In addition, it could be utilized as a marker of the inflammatory reaction during the neurodegeneration phase of AD (Sanfilippo et al, 2020 ; Brosseron et al, 2021 ).…”

“…In addition, it could be utilized as a marker of the inflammatory reaction during the neurodegeneration phase of AD (Sanfilippo et al, 2020;Brosseron et al, 2021).…”