Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of <i>SOD1</i> genotype

Zetterberg, Henrik; Jacobsson, Johan; Rosengren, Lars; Blennow, Kaj; Andersen, Peter M.

doi:10.1111/j.1468-1331.2007.01972.x

Cited by 128 publications

(104 citation statements)

References 28 publications

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“…Thus, the CSF concentration of NF-L mirrors the degree of acute axonal degradation. Elevated concentrations of neurofilament subunits have been described in many neurological diseases including Alzheimer's disease (Sjogren et al, 2000;Brettschneider et al, 2006), vascular dementia (Bjerke et al, 2009), amyotrophic lateral sclerosis (Zetterberg et al, 2007;Lu et al, 2012), and multiple sclerosis (Salzer et al, 2010). In multiple sclerosis, the CSF concentration of NF-L is downregulated by treatment with the anti-inflammatory drug natalizumab, indirectly implicating that increased CSF NF-L reflects inflammatory-mediated axonal damage (Gunnarsson et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Jakobsson

Bjerke

Ekman

et al. 2014

Neuropsychopharmacol

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Bipolar disorder (BD) is characterized by mood swings between manic and depressive states. The etiology and pathogenesis of BD is unclear, but many of the affected cognitive domains, as well as neuroanatomical abnormalities, resemble symptoms and signs of small vessel disease. In small vessel disease, cerebrospinal fluid (CSF) markers reflecting damages in different cell types and subcellular structures of the brain have been established. Hence, we hypothesized that CSF markers related to small vessel disease may also be applicable as biomarkers for BD. To investigate this hypothesis, we sampled CSF from 133 patients with BD and 86 healthy controls. The concentrations of neurofilament light chain (NF-L), myelin basic protein (MBP), S100B, and heart-type fatty acid binding protein (H-FABP) were measured in CSF and analyzed in relation to diagnosis, clinical characteristics, and ongoing medications. Hereby we found an elevation of the marker of subcortical axonal damage, NF-L, in bipolar subjects. We also identified positive associations between NF-L and treatment with atypical antipsychotics, MBP and lamotrigine, and H-FABP and lithium. These findings indicate axonal damage as an underlying neuropathological component of bipolar disorder, although the clinical value of elevated NF-L remains to be validated in follow-up studies. The associations between current medications and CSF brain injury markers might aid in the understanding of both therapeutic and adverse effects of these drugs.

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Section: Discussionmentioning

confidence: 99%

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Jakobsson

Bjerke

Ekman

et al. 2014

Neuropsychopharmacol

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“…Disease biomarkers provide a more effective therapy, since pharmacotherapy is most beneficial when given early in the course of MND. -15 506) and 175 (<125-710) ng/l, respectively, p<0.001] and correlated inversely with disease duration (spearman r= -0.518, p=0.001) 53 .…”

Section: Imagingmentioning

confidence: 93%

Amyotrophic lateral sclerosis (ALS): three letters that change the people's life. For ever

Oliveira

Pereira

2009

Arq. Neuro-Psiquiatr.

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-Amyotrophic lateral sclerosis (Als) is a neurodegenerative disease affecting the motor nervous system. it causes progressive and cumulative physical disabilities in patients, and leads to eventual death due to respiratory muscle failure. The disease is diverse in its presentation, course, and progression. We do not yet fully understand the cause or causes of the disease, nor the mechanisms for its progression; thus, we lack effective means for treating this disease. currently, we rely on a multidisciplinary approach to symptomatically manage and care for patients who have Als. Although amyotrophic lateral sclerosis and its variants are readily recognized by neurologists, about 10% of patients are misdiagnosed, and delays in diagnosis are common. prompt diagnosis, sensitive communication of the diagnosis, the involvement of the patient and their family, and a positive care plan are prerequisites for good clinical management. A multidisciplinary, palliative approach can prolong survival and maintain quality of life. Treatment with riluzole improves survival but has a marginal effect on the rate of functional deterioration, whereas non-invasive ventilation prolongs survival and improves or maintains quality of life. in this review, we discuss the diagnosis, management, and how to cope with impaired function and end of life on the basis of our experience, the opinions of experts, existing guidelines, and clinical trials. Multiple problems require a multidisciplinary approach including aggressive symptomatic management, rehabilitation to maintain motor function, nutritional support (enteric feeding, gastrostomy), respiratory support (non invasive home ventilation, invasive ventilation, tracheotomy), augmentative communication devices, palliative care, psychological support for both patients and families (because family members so often play a central role in management and care), communication between the care team, the patient and his or her family, and recognition of the clinical and social effects of cognitive impairment. social, bioethical, and financial issues as well as advance directives should be addressed. A plethora of evidence-based guidelines should be compiled into an internationally agreed guideline of best practice. The multidisciplinary team has changed the history of disease, with still no curative therapy available.KeY WorDs: amyotrophic lateral sclerosis, diagnosis, treatment.Esclerose lateral amiotrófica (ELA): três letras que mudam a vida de uma pessoa. Para sempre.Resumo -A esclerose lateral amiotrófica (elA) é doença neurodegenerativa comprometendo o sistema nervoso motor. ela causa comprometimento físico, progressivo e acumulativo, com óbito freqüentemente decorrente de falência respiratória. A enfermidade apresenta características diversas nas formas de apresentação, curso e progressão. Não entendemos ainda a causa ou causas dessa enfermidade, nem os mecanismos que regem a sua progressão; assim, tratamentos efetivos não são, até o momento, conhecidos. Atualmente, recomenda-se que os...

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“…Other studies have also sought to identify biomarkers in disorders associated with FTLD, including ALS and progressive supranuclear palsy (PSP). Potential biomarkers of ALS have included elevated levels of TDP-43, 12 inflammatory proteins (GM-CSF, 23 G-CSF, 23 MCP-1, 23,24 MIP1a/b, 23 and multiple interleukins including IL-2, IL-6, IL-8, IL-15, and IL-17 23,24 ), axonal structural proteins (neurofilament light chain 25 ), and growth factors (FGF basic protein and VEGF 23 ), and decreased levels of cystatin C, 26 insulin-like growth factor 1, 27 IL-10, 23 interferon-␥, 23 erythropoietin, 28 and angiotensin II. 29 While alterations in some biomarkers are likely specific for FTLD-TDP spectrum disorders, changes in many likely can occur in either FTLD-TDP or FTLD-tau.…”

Section: Figure 1 Box Plots Showing Median Values Quartiles and Outmentioning

confidence: 99%

“…29 While alterations in some biomarkers are likely specific for FTLD-TDP spectrum disorders, changes in many likely can occur in either FTLD-TDP or FTLD-tau. For example, neurofilament light chains were proposed as a biomarker for ALS, 25 but elevated levels were independently found in PSP and CBS. 30 Hence, any discovery or validation biomarker work in FTLD-TDP or FTLD-tau needs to incorporate both disorders comparatively with neuropathologic confirmation.…”

Section: Figure 1 Box Plots Showing Median Values Quartiles and Outmentioning

confidence: 99%

Novel CSF biomarkers for frontotemporal lobar degenerations

Chen‐Plotkin

Grossman³

et al. 2010

Neurology

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Objective: To identify antemortem CSF diagnostic biomarkers that can potentially distinguish between the 2 main causes of frontotemporal lobar degeneration (FTLD), i.e., FTLD with TDP-43 pathology (FTLD-TDP) and FTLD with tau pathology (FTLD-tau).Methods: CSF samples were collected antemortem from 23 patients with FTLD with known pathology to form a autopsy cohort as part of a comparative biomarker study that additionally included 33 living cognitively normal subjects and 66 patients with autopsy-confirmed Alzheimer disease (AD). CSF samples were also collected from 80 living patients clinically diagnosed with frontotemporal dementia (FTD). Levels of 151 novel analytes were measured via a targeted multiplex panel enriched in neuropeptides, cytokines, and growth factors, along with levels of CSF biomarkers for AD.Results: CSF levels of multiple analytes differed between FTLD-TDP and FTLD-tau, including Fas, neuropeptides (agouti-related peptide and adrenocorticotropic hormone), and chemokines (IL-23, IL-17). Classification by random forest analysis achieved high sensitivity for FTLD-TDP (86%) with modest specificity (78%) in the autopsy cohort. When the classification algorithm was applied to a living FTD cohort, semantic dementia was the phenotype with the highest predicted proportion of FTLD-TDP. When living patients with behavioral variant FTD were examined in detail, those predicted to have FTLD-TDP demonstrated neuropsychological differences vs those predicted to have FTLD-tau in a pattern consistent with previously reported trends in autopsy-confirmed cases. Conclusions:Clinical cases with FTLD-TDP and FTLD-tau pathology can be potentially identified antemortem by assaying levels of specific analytes that are well-known and readily measurable in CSF. Neurology ® 2010;75:2079-2086 GLOSSARY AD ϭ Alzheimer disease; AgRP ϭ Aguti-related protein; ANG-2 ϭ angiopoietin-2; ACTH ϭ adrenocorticotropic hormone; ALS ϭ amyotrophic lateral sclerosis; ApoB ϭ apolipoprotein B; bv-FTD ϭ behavioral variant FTD; CBS ϭ corticobasal syndrome; FTD ϭ frontotemporal dementia; FTLD ϭ frontotemporal lobar degeneration; FTLD-tau ϭ frontotemporal lobar degeneration with tau pathology; FTLD-TDP ϭ frontotemporal lobar degeneration with TDP-43 pathology; IL ϭ interleukin; MDC ϭ macrophage-derived chemokine; PNFA ϭ progressive nonfluent aphasia; PPA ϭ primary progressive aphasia; PSP ϭ progressive supranuclear palsy; S100b ϭ S100 calcium binding protein b; SemD ϭ semantic dementia; TRAIL-R3 ϭ tumor necrosis factor-related apoptosis-inducing ligand receptor 3.Frontotemporal lobar degeneration (FTLD) includes neurodegenerative disorders which lead to progressive behavioral or language abnormalities.1-3 There are 2 major forms of FTLD: FTLD-TDP with neuronal and glial inclusions immunoreactive to TAR DNA binding protein of ϳ43 kD (TDP-43), and FTLD-tau containing fibrillar and hyperphosphorylated tau inclusions.2,3 The main FTLD lesions likely reflect distinct disease mechanisms, 2 although antemortem diagnosis of the underlying path...

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Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of SOD1 genotype

Cited by 128 publications

References 28 publications

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Elevated Concentrations of Neurofilament Light Chain in the Cerebrospinal Fluid of Bipolar Disorder Patients

Amyotrophic lateral sclerosis (ALS): three letters that change the people's life. For ever

Novel CSF biomarkers for frontotemporal lobar degenerations

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