Cerebrospinal fluid erythropoietin (EPO) in amyotrophic lateral sclerosis

Brettschneider, Johannes; Widl, Karin; Schattauer, Dagmar; Ludolph, Albert C.; Tumani, Hayrettin

doi:10.1016/j.neulet.2007.02.002

Cited by 25 publications

(8 citation statements)

References 22 publications

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“…There are some promising CSF biomarker candidates in PD with α-synuclein as the most important and also in ALS (e.g. neurofilament heavy chain or erythropoietin) but they lack sensitivity and specificity [10], [13]–[17]. In CJD, there are already some CSF markers in use in combination with other diagnostic tools.…”

Section: Introductionmentioning

confidence: 99%

CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

et al. 2012

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BackgroundThe cyclic nucleotides cyclic adenosine-3′,5′-monophosphate (cAMP) and cyclic guanosine-3′,5′-monophosphate (cGMP) are important second messengers and are potential biomarkers for Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS) and Creutzfeldt-Jakob disease (CJD).Methodology/Principal FindingsHere, we investigated by liquid chromatography/tandem mass spectrometry (LC-MS/MS) the cerebrospinal fluid (CSF) concentrations of cAMP and cGMP of 82 patients and evaluated their diagnostic potency as biomarkers. For comparison with a well-accepted biomarker, we measured tau concentrations in CSF of CJD and control patients. CJD patients (n = 15) had lower cAMP (−70%) and cGMP (−55%) concentrations in CSF compared with controls (n = 11). There was no difference in PD, PD dementia (PDD) and ALS cases. Receiver operating characteristic (ROC) curve analyses confirmed cAMP and cGMP as valuable diagnostic markers for CJD indicated by the area under the curve (AUC) of 0.86 (cAMP) and 0.85 (cGMP). We calculated a sensitivity of 100% and specificity of 64% for cAMP and a sensitivity of 67% and specificity of 100% for cGMP. The combination of both nucleotides increased the sensitivity to 80% and specificity to 91% for the term cAMPxcGMP (AUC 0.92) and to 93% and 100% for the ratio tau/cAMP (AUC 0.99).Conclusions/SignificanceWe conclude that the CSF determination of cAMP and cGMP may easily be included in the diagnosis of CJD and could be helpful in monitoring disease progression as well as in therapy control.

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Section: Introductionmentioning

confidence: 99%

CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

et al. 2012

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“…Thus, the quest to identify informative CSF biomarkers for ALS, which would enable the early and reliable diagnosis of ALS, continues. For example, several potential CSF biomarkers identified for ALS include inflammatory proteins such as interferon gamma, granulocyte-macrophage colony stimulating factor, granulocyte colony stimulating factor, monocyte chemoattractant protein-1, macrophage inflammatory protein-1 a/b, and interleukins 2, 6, 8, 10, 15 and 17 (Kuhle et al, 2009; Mitchell et al, 2009), axonal proteins like neurofilament light and heavy chains (Brettschneider et al, 2006; Zetterberg et al, 2007), growth factors like insulin-like growth factor-1, erythropoietin and vascular endothelial growth factor (Bilic et al, 2006; Brettschneider et al, 2007; Mitchell et al, 2009), and angiotensin II (Kawajiri et al, 2009). However, further studies of these analytes are needed to confirm and extend our understanding of their potential diagnostic value for distinguishing ALS subjects from normal controls as well as from subjects with other neurodegenerative diseases in order to determine if changes in their CSF levels are specific to ALS or if they also occur in other neurological conditions.…”

Section: Introductionmentioning

confidence: 99%

On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia

Geser

Prvulovic

O’Dwyer

et al. 2011

Progress in Neurobiology

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Pathological 43-kDa transactive responsive sequence DNA-binding protein (TDP-43) has been recognized as the major disease protein in amyotrophic lateral sclerosis (ALS), frontotemporal lobar degeneration with ubiquitin positive, tau and α-synuclein negative inclusions (FTLD-U) and the transitional forms between these multisystem conditions. In order to develop TDP-43 into a successful ALS biomarker, the natural history of TDP-43 pathology needs to be characterized and the underlying pathophysiology established. Here we propose a spatial and temporal “two-axis” model of central nervous system vulnerability for TDP-43 linked degeneration and discuss recent studies on potential biomarkers related to pathological TDP-43 in the cerebrospinal fluid (CSF), blood, and skeletal muscle. The model includes the following “two arms”: First, a “motor neuron disease” or “spinal cord/brainstem to motor cortex” axis (with degeneration possibly ascending from the lower motor neurons to the upper motor neurons); and secondly, a “dementia” or “corticoid/allocortical to neocortex” axis (with a probable spread of TDP-43 linked degeneration from the mediotemporal lobe to wider mesocortical and neocortical brain areas). At the cellular level, there is a gradual disappearance of normal TDP-43 in the nucleus in combination with the formation of pathological aggregates in the cell body and cellular processes, which can also be used to identify the stage of the disease process. Moreover, TDP-43 lesions in subpial/subependymal or perivascular localizations have been noted in TDP-43 linked neurodegeneration, and this might account for increased CSF and blood TDP-43 levels through mechanisms that remain to be elucidated.

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“…EPO prevented neuronal injury and early motor neuron degeneration and delayed the onset of motor deterioration in female animals without prolonging survival [101]. EPO levels in the CSF have been reported to be decreased in ALS patients [102]. …”

Section: Protein Degradation Pathways and Sod1-clearing Agentsmentioning

confidence: 99%

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

Pandya

Zhu

et al. 2013

Cell. Mol. Life Sci.

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Amyotrophic lateral sclerosis (ALS) is a fatal chronic neurodegenerative disease whose hallmark is proteinaceous, ubiquitinated, cytoplasmic inclusions in motor neurons and surrounding cells. Multiple mechanisms proposed as responsible for ALS pathogenesis include dysfunction of protein degradation, glutamate excitotoxicity, mitochondrial dysfunction, apoptosis, oxidative stress, and inflammation. It is therefore essential to gain a better understanding of the underlying disease etiology and search for neuroprotective agents that might delay disease onset, slow progression, prolong survival, and ultimately reduce the burden of disease. Because riluzole, the only Food and Drug Administration (FDA)-approved treatment, prolongs the ALS patient’s life by only 3 months, new therapeutic agents are urgently needed. In this review, we focus on studies of various small pharmacological compounds targeting the proposed pathogenic mechanisms of ALS and discuss their impact on disease progression.

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Cerebrospinal fluid erythropoietin (EPO) in amyotrophic lateral sclerosis

Cited by 25 publications

References 22 publications

CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

CSF Concentrations of cAMP and cGMP Are Lower in Patients with Creutzfeldt-Jakob Disease but Not Parkinson's Disease and Amyotrophic Lateral Sclerosis

On the development of markers for pathological TDP-43 in amyotrophic lateral sclerosis with and without dementia

Therapeutic neuroprotective agents for amyotrophic lateral sclerosis

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