scholarly journals Serum Glial Fibrillary Acidic Protein (GFAP) Is a Marker of Disease Severity in Frontotemporal Lobar Degeneration

2020 ◽  
Vol 77 (3) ◽  
pp. 1129-1141 ◽  
Author(s):  
Alberto Benussi ◽  
Nicholas J. Ashton ◽  
Thomas K. Karikari ◽  
Stefano Gazzina ◽  
Enrico Premi ◽  
...  

Background: It is still unknown if serum glial fibrillary acidic protein (GFAP) is a useful marker in frontotemporal lobar degeneration (FTLD). Objective: To assess the diagnostic and prognostic value of serum GFAP in a large cohort of patients with FTLD. Methods: In this retrospective study, performed on 406 participants, we measured serum GFAP concentration with an ultrasensitive Single molecule array (Simoa) method in patients with FTLD, Alzheimer’s disease (AD), and in cognitively unimpaired elderly controls. We assessed the role of GFAP as marker of disease severity by analyzing the correlation with clinical variables, neurophysiological data, and cross-sectional brain imaging. Moreover, we evaluated the role of serum GFAP as a prognostic marker of disease survival. Results: We observed significantly higher levels of serum GFAP in patients with FTLD syndromes, except progressive supranuclear palsy, compared with healthy controls, but not compared with AD patients. In FTLD, serum GFAP levels correlated with measures of cognitive dysfunction and disease severity, and were associated with indirect measures of GABAergic deficit. Serum GFAP concentration was not a significant predictor of survival. Conclusion: Serum GFAP is increased in FTLD, correlates with cognition and GABAergic deficits, and thus shows promise as a biomarker of disease severity in FTLD.

2020 ◽  
Vol 91 (9) ◽  
pp. 960-967 ◽  
Author(s):  
Alberto Benussi ◽  
Thomas K Karikari ◽  
Nicholas Ashton ◽  
Stefano Gazzina ◽  
Enrico Premi ◽  
...  

ObjectiveTo assess the diagnostic and prognostic value of serum neurofilament light (NfL) and serum phospho-Tau181 (p-Tau181) in a large cohort of patients with frontotemporal lobar degeneration (FTLD).MethodsIn this retrospective study, performed on 417 participants, we analysed serum NfL and p-Tau181 concentrations with an ultrasensitive single molecule array (Simoa) approach. We assessed the diagnostic values of serum biomarkers in the differential diagnosis between FTLD, Alzheimer’s disease (AD) and healthy ageing; their role as markers of disease severity assessing the correlation with clinical variables, cross-sectional brain imaging and neurophysiological data; their role as prognostic markers, considering their ability to predict survival probability in FTLD.ResultsWe observed significantly higher levels of serum NfL in patients with FTLD syndromes, compared with healthy controls, and lower levels of p-Tau181 compared with patients with AD. Serum NfL concentrations showed a high accuracy in discriminating between FTLD and healthy controls (area under the curve (AUC): 0.86, p<0.001), while serum p-Tau181 showed high accuracy in differentiating FTLD from patients with AD (AUC: 0.93, p<0.001). In FTLD, serum NfL levels correlated with measures of cognitive function, disease severity and behavioural disturbances and were associated with frontotemporal atrophy and indirect measures of GABAergic deficit. Moreover, serum NfL concentrations were identified as the best predictors of survival probability.ConclusionsThe assessment of serum NfL and p-Tau181 may provide a comprehensive view of FTLD, aiding in the differential diagnosis, in staging disease severity and in defining survival probability.


2018 ◽  
Vol 26 (2) ◽  
pp. 210-219 ◽  
Author(s):  
Heidi Högel ◽  
Eero Rissanen ◽  
Christian Barro ◽  
Markus Matilainen ◽  
Marjo Nylund ◽  
...  

Background: Cerebrospinal fluid (CSF) levels of two soluble biomarkers, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL), have been shown to associate with multiple sclerosis (MS) disease progression. Now, both biomarkers can be detected reliably in serum, and importantly, their serum levels correlate well with their CSF levels. Objective: To evaluate the usability of serum GFAP measurement as a biomarker of progressive disease and disease severity in MS. Methods: Clinical course, Expanded Disability Status Scale (EDSS), disease duration, patient age and magnetic resonance imaging (MRI) parameters were reviewed in 79 MS patients in this cross-sectional hospital-based study. Serum samples were collected for measurement of GFAP and NfL concentrations using single molecule array (Simoa) assay. A cohort of healthy controls was evaluated for comparison. Results: Higher serum concentrations of both GFAP and NfL were associated with higher EDSS, older age, longer disease duration, progressive disease course and MRI pathology. Conclusion: Earlier studies have demonstrated that GFAP, unlike NfL, is not increased in association with acute focal inflammation-related nervous system damage. Our work suggests that GFAP serum level associates with disease progression in MS and could potentially serve as an easily measurable biomarker of central nervous system (CNS) pathology related to disease progression in MS.


2015 ◽  
Vol 53 (2) ◽  
pp. 1329-1342 ◽  
Author(s):  
Lu Yang ◽  
Honghong Yao ◽  
Xufeng Chen ◽  
Yu Cai ◽  
Shannon Callen ◽  
...  

2002 ◽  
Vol 22 (16) ◽  
pp. 6972-6979 ◽  
Author(s):  
Masaaki Takemura ◽  
Hiroshi Gomi ◽  
Emma Colucci-Guyon ◽  
Shigeyoshi Itohara

2021 ◽  
Author(s):  
Maren Freigang ◽  
Petra Steinacker ◽  
Claudia Diana Wurster ◽  
Olivia Schreiber-Katz ◽  
Alma Osmanovic ◽  
...  

Abstract BackgroundActivated astroglia is involved in the pathophysiology of neurodegenerative diseases and has also been described in animal models of spinal muscular atrophy (SMA). Given the urgent need of biomarkers for treatment monitoring of new RNA-modifying and gene replacement therapies in SMA, we examined glial fibrillary acidic protein (GFAP) concentrations as a marker of astrogliosis in the cerebrospinal fluid (CSF) of children and adult patients with SMA before and during treatment with nusinersen.Methods58 adult patients and 21 children with genetically confirmed 5q-associated SMA from 4 German motor neuron disease specialist care centers and 30 age- and sex-matched controls were prospectively included in this study. GFAP concentration was measured in CSF and motor performance and disease severity were assessed.ResultsCSF GFAP concentrations did not differ from controls but showed higher levels in more severely affected patients after adjustment for patients’ age. Within 14 months of nusinersen treatment, CSF GFAP concentrations did not change significantly.ConclusionsGFAP concentration in CSF of patients with long-standing SMA is not useful to assess disease severity or predict treatment response, but might support the hypothesis that glial activation is involved in SMA pathology.


Author(s):  
O. Z. Yaremchuk ◽  
K. A. Posokhova ◽  
O. S. Tokarskyi

The study aims to investigate the infuence of L-arginine on the content of nitrite anions (NO2¯) and nitrate anions (NO3¯) and the content of glial fibrillary acidic protein (GFAP) in the cerebellum and cerebral hemispheres of BALB/c mice with antiphospholipid syndrome. The studies were performed on 30 female BALB/c mice. The experimental animals were divided into 3 groups: 1 – control (intact) animals; 2 – animals with experimental antiphospholipid syndrome (APS), 3 – animals with APS, which were injected with L-arginine at a dose of 25 mg/kg, intraperitoneally once a day, for 10 consecutive days after the development of APS. The increase in glial fibrillary acidic protein and stable metabolites of nitric oxide NO2¯ and NO3¯ in the cerebellum and cerebral hemispheres, relative to the control, was observed in APS-developed BALB/c mice. In case of injection of the precursor of NO synthesis, L-arginine, animals with APS were found to have a further significant increase in the content of NO2¯ and NO3¯ in the cerebellum and the cerebral hemispheres. The introduction of L-arginine did not cause significant changes in GFAP (total) in cerebral hemispheres. However, GFAP content (49-37 kDa) was decreasing. The cerebellum showed an increase in GFAP (total) and GFAP (49-37 kDa) content, compared to the performance of animals with APS. Therefore, the increase in the content of GFAP in the cerebellum and the cerebral hemispheres of BALB/c mice under APS indicates the development of reactive astrogliosis. The introduction of the precursor of NO synthesis, L-arginine, is accompanied by an increase in the content of stable metabolites of nitric oxide (NO2¯, NO3¯) and GFAP in the cerebellum of BALB/c mice, which can indirectly confirm the role of NO in regulating of GFAP expression in astrocytes under APS.


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