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Boch, C.

Publications and source records attributed to Boch, C..

2 recordsLinked to original sources

Exploration of novel biomarkers for neurodegenerative diseases using proteomic analysis and ligand-binding assays

Neurodegenerative diseases are a major cause of morbidity and mortality world-wide, and their public health burden continues to increase. There is an urgent need to develop reliable and sensitive biomarkers to aid the timely diagnosis, disease progression monitoring, and therapeutic development for neurodegenerative disorders. Proteomic screening strategies, including antibody microarrays, are a powerful tool for biomarker discovery, but their findings should be confirmed using quantitative assays. The current study explored the feasibility of combining an exploratory proteomic strategy and confirmatory ligand-binding assays to screen for and validate biomarker candidates for neurodegenerative disorders. It analyzed cerebrospinal fluid (CSF) and plasma samples from patients with Alzheimers disease, Parkinsons disease, and multiple sclerosis and healthy controls. The screening antibody microarray identified differentially expressed proteins between patients with neurodegenerative diseases and healthy controls. Quantitative ligand-binding assays confirmed that cluster of differentiation 14 (CD14) levels were elevated in CSF of patients with Alzheimers disease, whereas osteopontin levels were increased in CSF of patients with Parkinsons disease. The current study demonstrated the utility of combining an exploratory proteomic approach and quantitative ligandbinding assays to identify biomarker candidates for neurodegenerative disorders. To further validate and expand these findings, large-scale analyses using well characterized samples should be conducted.

neuroscience↗

GDF15 is a dynamic biomarker of the Integrated Stress Response in the central nervous system

AimCharacterize Growth Differentiation Factor 15 (GDF15) as a secreted biomarker of the Integrated Stress Response (ISR) within the Central Nervous System (CNS). MethodsWe determined GDF15 levels utilizing in vitro and in vivo neuronal systems wherein the ISR was activated. Primarily, we used the murine model of Vanishing White Matter disease (VWMD), a neurological disease driven by persistent ISR in the CNS, to establish a link between levels of GDF15 in the cerebrospinal fluid (CSF) and ISR gene expression signature in the CNS. GDF15 was also determined in the CSF of VWM patients. ResultsGDF15 expression was increased concomitant to ISR activation in stress-induced primary astrocytes as well as in retinal ganglion cells following optic nerve crush, while treatment with 2Bact, a specific eIF2B activator, suppressed both the ISR and GDF15. In the VWMD model, CSF GDF15 levels corresponded with the magnitude of the ISR and were reduced by 2BAct. In VWM patients, mean CSF GDF15 was elevated >20-fold as compared to healthy controls, whereas plasma GDF15 was undifferentiated. ConclusionsThese data suggest that CSF GDF15 is a dynamic marker of ISR activation in the CNS and may serve as a pharmacodynamic biomarker for ISR-modulating therapies.

neuroscience↗