Cerebrospinal fluid levels of chromogranin A and phosphorylated neurofilament heavy chain are elevated in amyotrophic lateral sclerosis

Kaiserová, Michaela; Grambalova, Zuzana; Otruba, Pavel; Stejskal, David; Vránová, Hana Přikrylová; Mares, Jan; Menšíková, Kateřina; Kaňovský, Petr

doi:10.1111/ane.12735

Cited by 14 publications

(9 citation statements)

References 23 publications

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“…In addition to AD [34], CHGA also accumulates in brain areas with neuronal degeneration in Parkinson´s [39] and Pick´s disease [40], suggesting that this protein could be a useful biomarker for various neurological disorders. In fact, the potential of CHGA as biomarker in CSF has been investigated in prion-like neurodegenerative diseases such as AD [34] or amyotrophic lateral sclerosis [41]. Although we did not find statistical differences of CHGA concentrations in the CSF of scrapie sheep and its upregulation in other neurodegenerative diseases diminishes its potentiality as a prion biomarker, data in the CNS of both scrapie models indicate that expression of this protein is a key feature also in prion diseases.…”

Section: Discussioncontrasting

confidence: 60%

BAMBI and CHGA in Prion Diseases: Neuropathological Assessment and Potential Role as Disease Biomarkers

et al. 2020

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Prion diseases affect both animals and humans. Research in the natural animal model of the disease could help in the understanding of neuropathological mechanisms and in the development of biomarkers for human pathologies. For this purpose, we studied the expression of 10 genes involved in prion propagation in vitro in the central nervous system of scrapie-infected sheep. Dysregulated genes (BAMBI and CHGA) were further analysed in a transgenic murine model (Tg338) of scrapie, and their protein distribution was determined using immunohistochemistry and Western blot. Their potential as biomarkers was finally assessed using enzyme-linked immunosorbent assay (ELISA) in cerebrospinal fluid (CSF) of scrapie sheep and Creutzfeldt-Jakob disease (CJD) patients. Protein BAMBI was upregulated in highly affected brain areas and CHGA was overexpressed along the brain in both models. Moreover, BAMBI and CHGA immunostaining scores strongly correlated with spongiosis and microgliosis in mice. Finally, levels of BAMBI were significantly higher in the CSF of clinical sheep and CJD patients. In addition to their potential as biomarkers, our work confirms the role of BAMBI and CHGA in prion neuropathology in vivo, but besides prion replication, they seem to be involved in the characteristic neuroinflammatory response associated to prion infection.

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Section: Discussioncontrasting

confidence: 60%

BAMBI and CHGA in Prion Diseases: Neuropathological Assessment and Potential Role as Disease Biomarkers

et al. 2020

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“…Changes in the levels of these synapse-related proteins are not unique to AD; they have also been detected in other neurological disorders, such as multiple sclerosis 28 , schizophrenia 29 , Parkinson's disease 30 , and amyotrophic lateral sclerosis (ALS) 31,32 . Consistent with these findings, we also found diminished CSF levels of VGF, CgA, and Sg1 in subjects with other brain disorders (e.g., frontotemporal dementia, Parkinson's disease, and cerebrovascular disease).…”

Section: Discussionmentioning

confidence: 99%

SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease

Park

Jung

Park

et al. 2020

Sci Rep

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Cerebrospinal fluid (CSF) Aβ42 and tau protein levels are established diagnostic biomarkers of Alzheimer's disease (AD). However, their inadequacy to represent clinical efficacy in drug trials indicates the need for new biomarkers. Sequential window acquisition of all theoretical fragment ion spectra (SWATH)-based mass spectrometry (MS) is an advanced proteomic tool for large-scale, high-quality quantification. In this study, SWATH-MS showed that VGF, chromogranin-A, secretogranin-1, and opioid-binding protein/cell adhesion molecule were significantly decreased in 42 AD patients compared to 39 controls, whereas 14-3-3ζ was increased (FDR < 0.05). In addition, 16 other proteins showed substantial changes (FDR < 0.2). The expressions of the top 21 analytes were closely interconnected, but were poorly correlated with CSF Aβ42, tTau, and pTau181 levels. Logistic regression analysis and data mining were used to establish the best algorithm for AD, which created novel biomarker panels with high diagnostic value (AUC = 0.889 and 0.924) and a strong correlation with clinical severity (all p < 0.001). Targeted proteomics was used to validate their usefulness in a different cohort (n = 36) that included patients with other brain disorders (all p < 0.05). This study provides a list of proteins (and combinations thereof) that could serve as new AD biomarkers. Cerebrospinal fluid (CSF) levels of Aβ1-42 (Aβ42), total Tau (tTau), and phosphorylated Tau181 (pTau181) are diagnostic markers of Alzheimer's disease (AD) 1,2. These biomarkers are currently used to confirm the core pathology of AD, i.e., Aβ and tau pathology, in deceased patients while they are alive 3 , and are also monitored in AD therapeutic trials 4. However, accumulating evidence has demonstrated a lack of utility of these markers after clinical onset of AD due to early concentration plateaus 5 and poor reflection of the clinical benefits of therapeutics that target them 6. CSF proteins related to synaptic function, neurodegeneration, inflammation, and Aβ metabolism have recently been suggested as supplementary biomarkers 7 ; however, they have not yet been clinically adopted.

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“…This protein is present in both the peripheral and the central nervous system [1]. CgA is known as a marker of neuroendocrine tumors [2], but it is also studied as a potential marker of other diseases, including essential hypertension [3] and various neurological diseases such as Alzheimer's disease [4] and amyotrophic lateral sclerosis [5]. Recent studies show that CgA levels may also be altered in patients with Parkinson's disease (PD), in both serum and cerebrospinal fluid (CSF) [6][7][8][9][10].…”

Section: Introductionmentioning

confidence: 99%

Cerebrospinal Fluid Levels of Chromogranin A in Parkinson’s Disease and Multiple System Atrophy

et al. 2021

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Background: Chromogranin A (CgA) and other peptides from the chromogranin–secretogranin family have been recently studied as potential biomarkers of various neurodegenerative diseases, including Parkinson’s disease (PD). Methods: We measured CgA in the cerebrospinal fluid (CSF) of 119 PD patients, 18 multiple system atrophy (MSA) patients, and 31 age-matched controls. We also correlated the values with disease duration and levodopa dose equivalent. Results: In the PD patients, CSF CgA tended to be lower than the control group (median 124.5 vs. 185.2 µg/L; p = 0.057); however, the results did not reach statistical significance. CSF CgA levels in MSA were significantly lower compared to the control group (median 104.4 vs. 185.2; p = 0.014). There was no significant difference in CSF CgA between PD and MSA patients (p = 0.372). There was no association between CSF CgA and disease duration or levodopa dose equivalent in PD or in MSA. Conclusions: We observed a tendency toward lower CSF CgA levels in both PD and MSA compared to the control group; however, the difference reached statistical significance only in MSA. Based on these results, CgA may have potential as a biomarker in PD and MSA, but further studies on larger numbers of patients are needed to draw conclusions.

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Cerebrospinal fluid levels of chromogranin A and phosphorylated neurofilament heavy chain are elevated in amyotrophic lateral sclerosis

Abstract: Identifying CSF biomarkers in ALS is important in order to establish the diagnosis in the early stages of the disease. pNF-H seems to be a good biomarker for the diagnosis of ALS. If confirmed on a larger group of patients, CgA may also become useful in the diagnosis of sporadic ALS.

Cited by 14 publications

References 23 publications

BAMBI and CHGA in Prion Diseases: Neuropathological Assessment and Potential Role as Disease Biomarkers

BAMBI and CHGA in Prion Diseases: Neuropathological Assessment and Potential Role as Disease Biomarkers

SWATH-MS analysis of cerebrospinal fluid to generate a robust battery of biomarkers for Alzheimer’s disease

Cerebrospinal Fluid Levels of Chromogranin A in Parkinson’s Disease and Multiple System Atrophy

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