CSF nonphosphorylated Tau as a biomarker for the discrimination of <scp>AD</scp> from <scp>CJD</scp>

Ermann, Natalia; Lewczuk, Piotr; Schmitz, Matthias; Lange, Peter; Knipper, Tobias; Goebel, Stefan; Kornhuber, Johannes; Zerr, Inga; Llorens, Franc

doi:10.1002/acn3.584

Cited by 15 publications

(7 citation statements)

References 12 publications

(17 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of phosphorylation, it is less clear if it is necessary for inducing propagation. Most studies reported that extracellular tau presents low levels of phosphorylation, an observation recently confirmed in human CSF (Le et al, 2012; Mohamed et al, 2014; Lewczuk et al, 2017; Rodriguez et al, 2017; Wang et al, 2017; Ermann et al, 2018). Aggregates composed of non-phosphorylated recombinant tau were shown to induce tau propagation (Wu et al, 2012; Mirbaha et al, 2015).…”

Section: How the Elucidation Of Tau Secretory Pathways And The Characmentioning

confidence: 78%

“…However, in culture medium, most studies reported that tau presents either no phosphorylation or low phosphorylation levels (Mohamed et al, 2014; Rodriguez et al, 2017; Wang et al, 2017). More recently, two studies reported that an important amount of tau in the CSF of AD patients is not phosphorylated (Lewczuk et al, 2017; Ermann et al, 2018). In the case of tau aggregation, most studies did not report the presence of aggregated tau in culture medium and CSF.…”

Section: Extracellular Tau Forms: Secreted Tau Vs Csf-taumentioning

confidence: 99%

See 1 more Smart Citation

Tau Secretion: Good and Bad for Neurons

2019

View full text Add to dashboard Cite

In Alzheimer’s disease (AD), neurofibrillary tangles (NFTs), lesions composed of hyperphosphorylated and aggregated tau, spread from the transentorhinal cortex to the hippocampal formation and neocortex. Growing evidence indicates that tau pathology propagates trans- synaptically, implying that pathological tau released by pre-synaptic neurons is taken up by post-synaptic neurons where it accumulates and aggregates. Observations such as the presence of tau in the cerebrospinal fluid (CSF) from control individuals and in the CSF of transgenic mice overexpressing human tau before the detection of neuronal death indicate that tau can be secreted by neurons. The increase of tau in the CSF in pathological conditions such as AD suggests that tau secretion is enhanced and/or other secretory pathways take place when neuronal function is compromised. In physiological conditions, extracellular tau could exert beneficial effects as observed for other cytosolic proteins also released in the extracellular space. In such a case, blocking tau secretion could have negative effects on neurons unless the mechanism of tau secretion are different in physiological and pathological conditions allowing the prevention of pathological tau secretion without affecting the secretion of physiological tau. Furthermore, distinct extracellular tau species could be secreted in physiological and pathological conditions, species having the capacity to induce tau pathology being only secreted in the latter condition. In the present review, we will focus on the mechanisms and function of tau secretion in both physiological and pathological conditions and how this information can help to elaborate an efficient therapeutic strategy to prevent tau pathology and its propagation.

show abstract

Section: How the Elucidation Of Tau Secretory Pathways And The Characmentioning

confidence: 78%

Section: Extracellular Tau Forms: Secreted Tau Vs Csf-taumentioning

confidence: 99%

Tau Secretion: Good and Bad for Neurons

2019

View full text Add to dashboard Cite

show abstract

“…CSF is in direct contact with the brain parenchyma and can indirectly reflect certain pathological indications of the central nervous system (10). Changes in the abundance of many proteins (14-3-3 protein, tau et al) in CSF can be used in the diagnosis of CJD (11–14). RT-QuIC has proved to be a very valuable diagnostic CSF test for sCJD (7).…”

Section: Introductionmentioning

confidence: 99%

Detection of Cell-Free Mitochondrial DNA in Cerebrospinal Fluid of Creutzfeldt-Jakob Patients

Duan

Zhao

et al. 2019

Front. Neurol.

View full text Add to dashboard Cite

Background: The current diagnosis method for Creutzfeldt-Jakob disease (CJD) is post-mortem examination, so early detection of CJD has been historically problematic. Auxiliary detection of CJD based on changes in levels of components of the cerebrospinal fluid (CSF) has become a focus of research. In other neurodegenerative diseases such as Alzheimer's disease (AD), cell-free mitochondrial DNA (mtDNA) in the CSF of patients may serve as a biomarker that could facilitate early diagnosis and studies of the mechanisms underlying the disease. Methods: In this study, the cell-free mitochondrial DNA in the CSF of patients with sCJD and control patients was compared by digital droplet PCR. Results: The cell-free mitochondrial DNA copy number in the CSF of sCJD patients was significantly increased in comparison with that of the control group, and this difference was pathologically related to CJD. Conclusion: Therefore, we speculate that changes in cerebrospinal fluid mitochondrial DNA copy number play an important role in the study of CJD mechanism and diagnosis.

show abstract

“…Another tau related biomarker, non-phospho-Tau (non-P-Tau), was found to be significantly elevated in CJD (3683 ± 3599 pg/mL) compared to AD (148 ± 219 pg/mL) and neurological controls (62 ± 40 pg/mL). Non-P-Tau also significantly improved differentiation of CJD from AD (99%) compared to total-Tau (90%), P-Tau (62%) and 14-3-3 (91%) [ 44 ].…”

Section: Markers For Rapid Neurodegenerationmentioning

confidence: 99%

Clinical Use of Improved Diagnostic Testing for Detection of Prion Disease

Figgie

Appleby

2021

Viruses

View full text Add to dashboard Cite

Prion diseases are difficult to recognize as many symptoms are shared among other neurologic pathologies and the full spectra of symptoms usually do not appear until late in the disease course. Additionally, many commonly used laboratory markers are non-specific to prion disease. The recent introduction of second-generation real time quaking induced conversion (RT-QuIC) has revolutionized pre-mortem diagnosis of prion disease due to its extremely high sensitivity and specificity. However, RT-QuIC does not provide prognostic data and has decreased diagnostic accuracy in some rarer, atypical prion diseases. The objective of this review is to provide an overview of the current clinical utility of fluid-based biomarkers, neurodiagnostic testing, and brain imaging in the diagnosis of prion disease and to suggest guidelines for their clinical use, with a focus on rarer prion diseases with atypical features. Recent advancements in laboratory-based testing and imaging criteria have shown improved diagnostic accuracy and prognostic potential in prion disease, but because these diagnostic tests are not sensitive in some prion disease subtypes and diagnostic test sensitivities are unknown in the event that CWD transmits to humans, it is important to continue investigations into the clinical utility of various testing modalities.

show abstract

CSF nonphosphorylated Tau as a biomarker for the discrimination of AD from CJD

Cited by 15 publications

References 12 publications

Tau Secretion: Good and Bad for Neurons

Tau Secretion: Good and Bad for Neurons

Detection of Cell-Free Mitochondrial DNA in Cerebrospinal Fluid of Creutzfeldt-Jakob Patients

Clinical Use of Improved Diagnostic Testing for Detection of Prion Disease

Contact Info

Product

Resources

About