CSF and Blood Levels of GFAP in Alexander Disease

Jany, Paige L.; Agosta, Guillermo; Benko, William; Eickhoff, Jens; Keller, Stephanie; Köehler, Wolfgang; Koeller, David M.; Mar, Soe; Naidu, Sakkubai; Ness, Jayne; Pareyson, Davide; Renaud, Deborah L.; Salsano, Ettore; Schiffmann, Raphael; Simon, Julie; Vanderver, Adeline; Eichler, Florian; Knaap, Marjo S. van der; Messing, Albee

doi:10.1523/eneuro.0080-15.2015

Cited by 36 publications

(31 citation statements)

References 49 publications

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“…As we already described in the Introduction above, a number of previous studies support that GFAP is correlated to specific conditions in patients with various neurodegenerative diseases ( 11 – 15 , 18 , 19 , 30 ). Additionally, GFAP levels considerably increased in CSF from patients suffering from Alexander disease ( 30 ), a genetic disorder caused by mutations in the GFAP gene, leading to myelin abnormalities in the midbrain and cerebellum ( 31 ). These studies support the idea that GFAP could be classified as a diagnostic biomarker in patients with neurological disease conditions.…”

Section: Discussionsupporting

confidence: 55%

Blood Level of Glial Fibrillary Acidic Protein (GFAP) Does not Correlate With Disease Progression in a Rat Model of Familial ALS (SOD1G93A Transgenic)

2018

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Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by specific loss of motor neurons in the spinal cord and brain stem. Currently, there are limited options for treating ALS and further investigation of the disease etiology and ALS disease progression need to be completed. There is an urgent need to identify biomarkers to detect and study disease progression in ALS. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is expressed by a number of cells related to the central nervous system including glial cells and ependymal cells. Recent studies indicated that significant levels of GFAP protein were detected in peripheral tissues, such as skeletal muscle. In this study, we hypothesized that levels of GFAP in blood represent a biomarker of disease progression in ALS. To test this specific hypothesis, we used a rat model of familial ALS (SOD1G93A transgenic), which has been extensively used to understand the complexity of this devastating disease. Disease progression in a cohort of male and female SOD1G93A transgenic rats was monitored by motor function, and blood samples were collected when these animals reached disease end-stage. We measured GFAP protein levels by ELISA and found no correlation between GFAP concentration and disease progression in either serum and plasma samples of SOD1G93A transgenic. Further investigation would be required in order to implicate blood GFAP as a potential biomarker for ALS.

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Section: Discussionsupporting

confidence: 55%

Blood Level of Glial Fibrillary Acidic Protein (GFAP) Does not Correlate With Disease Progression in a Rat Model of Familial ALS (SOD1G93A Transgenic)

2018

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“…Thus the genetic evidence suggests a critical role of elevations in total GFAP levels in the disease pathogenesis. Indeed, increased GFAP levels were consistently found in AxD patients both when measured in brain parenchyma (Walker et al ., 2014) and in cerebrospinal fluid (Jany et al ., 2015). The accumulation of GFAP that is found in AxD results in part from increased mRNA synthesis (Hagemann et al ., 2005), and there is a spontaneous increase in the activity of the GFAP promoter (Jany et al ., 2013).…”

Section: Introductionmentioning

confidence: 99%

The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP

Lin

Huang

Opal

et al. 2016

MBoC

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“…Although the absolute biomarker levels were different compared to in vivo conditions, the ratio of circulation:chamber levels was comparable to human blood:CSF ratios [48][49][50][51][52] . Thus, our model offers the potential to study how specific protein levels correlate in "brain" to "blood" compartments to understand the dependence and independence among biomarkers.…”

Section: Discussionmentioning

confidence: 99%

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases

Robert

Weilinger

Zao

et al. 2020

Preprint

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Introduction: The neurovascular unit (NVU) – the interaction between the neurons and the cerebrovasculature – is increasingly important to interrogate through human-based experimental models. Although advanced models of cerebral capillaries have been developed in the last decade, there is currently noin vitro3-dimensional (3D) perfusible model of the human cortical arterial NVU. Method: We used a tissue-engineering technique to develop a scaffold-directed, perfusible, 3D human NVU that is cultured in native-like flow conditions that mimics the anatomy and physiology of cortical penetrating arteries. Results: This system, composed of primary human vascular cells (endothelial cells, smooth muscle cells and astrocytes) and induced pluripotent stem cell (iPSC) derived neurons, demonstrates a physiological multilayer organization of the involved cell types. It also reproduces key characteristics of cortical neurons and astrocytes, as well as the formation of a selective and functional endothelial barrier. We further provide proof-of-principle that our in vitro human arterial NVU may be suitable to study neurodegenerative diseases such as Alzheimer’s disease (AD), as we report both phosphorylated tau and beta-amyloid accumulation in our model over time. Finally, we show that our arterial NVU model enables the study of neuronal and glial fluid biomarkers. Conclusion: This model is a suitable tool to investigate arterial NVU functions such as neuronal electrophysiology in health and disease. Further the design of platform allows culture under native-like flow conditions for extended periods of time and yields sufficient tissue and media for downstream immunohistochemistry and biochemistry analyses.

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CSF and Blood Levels of GFAP in Alexander Disease

Cited by 36 publications

References 49 publications

Blood Level of Glial Fibrillary Acidic Protein (GFAP) Does not Correlate With Disease Progression in a Rat Model of Familial ALS (SOD1G93A Transgenic)

Blood Level of Glial Fibrillary Acidic Protein (GFAP) Does not Correlate With Disease Progression in a Rat Model of Familial ALS (SOD1G93A Transgenic)

The role of gigaxonin in the degradation of the glial-specific intermediate filament protein GFAP

An in vitro bioengineered model of the human arterial neurovascular unit to study neurodegenerative diseases

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