TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

Steinacker, Petra; Hendrich, Corinna; Sperfeld, Anne D.; Jesse, Sarah; Arnim, Christine A. F. Von; Lehnert, Stefan; Pabst, Alice; Uttner, Ingo; Tumani, Hayrettin; Lee, Virginia M.‐Y.; Trojanowski, John Q.; Kretzschmar, Hans A.; Ludolph, Albert C.; Neumann, Manuela; Otto, Markus

doi:10.1001/archneur.65.11.1481

Cited by 176 publications

(130 citation statements)

References 33 publications

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“…In postmortem studies, TDP-43 inclusions are detected in approximately 97% of patients with ALS. Based on these findings, investigators have pursued TDP-43 as a biofluid biomarker for ALS [92][93][94][95]. If changes can be reliably detected in blood or CSF, TDP-43 could be a valuable biomarker for the majority of patients with ALS.…”

Section: Tar Dna-binding Protein Of 43 Kdamentioning

confidence: 99%

“…In addition, TDP-43 has been shown to be subject to alternative splicing causing truncations of the N-or C-terminus, leading to splice variants linked to ALS [96]. TDP-43 has been detected as 2 distinct species via Western blot: a 45-kDa (phosphorylated form) and 28-kDa isoform [95]. However, the 28-kDa isoform was determined to be nonspecific binding to IgG light chain, indicating antibody cross-reactivity.…”

Section: Tar Dna-binding Protein Of 43 Kdamentioning

confidence: 99%

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Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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Amyotrophic lateral sclerosis (ALS) is a highly heterogeneous disease with no effective treatment. Drug development has been hampered by the lack of biomarkers that aid in early diagnosis, demonstrate target engagement, monitor disease progression, and can serve as surrogate endpoints to assess the efficacy of treatments. Fluid-based biomarkers may potentially address these issues. An ideal biomarker should exhibit high specificity and sensitivity for distinguishing ALS from control (appropriate disease mimics and other neurologic diseases) populations and monitor disease progression within individual patients. Significant progress has been made using cerebrospinal fluid, serum, and plasma in the search for ALS biomarkers, with urine and saliva biomarkers still in earlier stages of development. A few of these biomarker candidates have demonstrated use in patient stratification, predicting disease course (fast vs slow progression) and severity, or have been used in preclinical and clinical applications. However, while ALS biomarker discovery has seen tremendous advancements in the last decade, validating biomarkers and moving them towards the clinic remains more elusive. In this review, we highlight biomarkers that are moving towards clinical utility and the challenges that remain in order to implement biomarkers at all stages of the ALS drug development process.

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Section: Tar Dna-binding Protein Of 43 Kdamentioning

confidence: 99%

Section: Tar Dna-binding Protein Of 43 Kdamentioning

confidence: 99%

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Bowser

2017

Neurotherapeutics

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“…Our studies focus on TDP-43 as a biological marker in CSF. As TDP-43 is mainly found in sporadic ALS cases and signifi cantly higher levels of TDP-43 are found in their CSF when compared with age-matched controls [44] , we decided to investigate these patients in a proof-of-principle type of manner, as here the neuropathology can be easier predicted compared with the other diagnosis of the FTLD spectrum, especially the bvFTD cases [37] . This included FTLD, FTLD + ALS and ALS cases.…”

Section: Other Neurochemical Markers For the Diagnosis Of Ftldmentioning

confidence: 99%

Recent biomarker approaches in the diagnosis of frontotemporal lobar degeneration/Neurochemische Ansätze in der Diagnose der Frontotemporalen Lobärdegeneration

Feneberg

Steinacker

Lehnert

et al. 2012

LaboratoriumsMedizin

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Frontotemporal lobar degeneration (FTLD) is a heterogeneous group of syndromes with different symptoms. Frontotemporal lobar degeneration is mostly used as a clinical umbrella term for different diseases. In some clinical subtypes of the FTLD spectrum, a close correlation with underlying pathology can be found. Neuroimaging techniques, such as magnetic resonance imaging and position emission tomography help to detect neuroanatomical lesions and therefore obtain relevance for in vivo prediction of neurodegeneration. However, there is still a lack of neurochemical biomarkers helping to differentiate between underlying histopathologies. The following review gives an overview about present neurochemical biomarker studies and perspective approaches in the diagnosis of FTLD.

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“…However, structural MRI and FDG PET are more accurate than amyloid imaging in predicting cognitive status [48] . Ligands targeting the paired helical filament form (PHF) of tau, specific to AD have been developed and are currently close to market [49][50][51] .…”

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confidence: 99%

What can imaging tell us about cognitive impairment and dementia?

Narayanan

Murray

2016

WJR

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Dementia is a contemporary global health issue with far reaching consequences, not only for affected individuals and their families, but for national and global socioeconomic conditions. The hallmark feature of dementia is that of irreversible cognitive decline, usually affecting memory, and impaired activities of daily living. Advances in healthcare worldwide have facilitated longer life spans, increasing the risks of developing cognitive decline and dementia in late life. Dementia remains a clinical diagnosis. The role of structural and molecular neuroimaging in patients with dementia is primarily supportive role rather than diagnostic, American and European guidelines recommending imaging to exclude treatable causes of dementia, such as tumor, hydrocephalus or intracranial haemorrhage, but also to distinguish between different dementia subtypes, the commonest of which is Alzheimer's disease. However, this depends on the availability of these imaging techniques at individual centres. Advanced magnetic resonance imaging (MRI) techniques, such as functional connectivity MRI, diffusion tensor imaging and magnetic resonance spectroscopy, and molecular imaging techniques, such as 18F fluoro-deoxy glucose positron emission tomography (PET), amyloid PET, tau PET, are currently within the realm of dementia research but are available for clinical use. Increasingly the research focus is on earlier identification of at risk preclinical individuals, for example due to family history. Intervention at the preclinical stages before irreversible brain damage occurs is currently the best hope of reducing the impact of dementia.

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TDP-43 in Cerebrospinal Fluid of Patients With Frontotemporal Lobar Degeneration and Amyotrophic Lateral Sclerosis

Cited by 176 publications

References 33 publications

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Fluid-Based Biomarkers for Amyotrophic Lateral Sclerosis

Recent biomarker approaches in the diagnosis of frontotemporal lobar degeneration/Neurochemische Ansätze in der Diagnose der Frontotemporalen Lobärdegeneration

What can imaging tell us about cognitive impairment and dementia?

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