Increased tau protein level in postmortem cerebrospinal fluid

Morita, Takashi; Kudo, Takashi; Ikura, Yuji; Kashiwagi, Yujiro; Miyamae, Yasuyuki; Nakamura, Yu; Tanaka, Toshihisa; Shinozaki, Kazuo; Nishikawa, Takashi; Takeda, Masatoshi

doi:10.1111/j.1440-1819.1998.tb00981.x

Cited by 18 publications

(10 citation statements)

References 15 publications

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“…The lower total protein concentration of Alzheimer's CSF may account for the lower concentrations of extracellular chaperones in Alzheimer's CSF found in this study, suggesting that extracellular chaperones are not selectively depleted from this fluid. This is consistent with previous work showing that Alzheimer's disease patient CSF has a lower total protein concentration than normal CSF controls (Morihara et al 1998). In contrast, previous studies suggested that the concentration of at least one of the extracellular chaperones, clusterin, is not lower in Alzheimer's CSF (Lidstrom et al 2001;Nilselid et al 2006).…”

Section: Discussionsupporting

confidence: 82%

Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on Aβ1-42 toxicity and uptake

Yerbury

Wilson

2010

Cell Stress and Chaperones

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Section: Discussionsupporting

confidence: 82%

Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on Aβ1-42 toxicity and uptake

Yerbury

Wilson

2010

Cell Stress and Chaperones

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“…In general, human tau is mostly absent from CSF. However, neuron destruction in neurodegenerative diseases such as AD releases human tau into the CSF [29]. Human tau levels are thus an indicator of nerve degeneration, and can be used to rule out psychiatric disorders unaccompanied by nerve degeneration, such as dementia and depression.…”

Section: Discussionmentioning

confidence: 99%

“…It is well established that the tau protein is a marker for neuronal cell death [29]. In group B (LRG ≥ 67 ng/ml, tau ≥ 200 pg/ml), this indicated either a more advanced iNPH with irreversible neurologic symptoms or co-existing neurodegenerative disorders like a AD.…”

Section: Discussionmentioning

confidence: 99%

Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus

et al. 2011

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ObjectiveCerebrospinal fluid (CSF) shunting can improve symptoms of elderly patients' idiopathic normal pressure hydrocephalus (iNPH). However, adjunctive means for confirming the diagnosis remain unavailable. We have previously reported the specific increase of leucine-rich alpha-2-glycoprotein (LRG) in iNPH CSF, and the present study investigates its potential clinical applications.MethodsWe performed CSF tap test (TT) on 90 patients (mean age 73.4 years) and shunting in 52 patients (mean age 73.5 years), evaluating symptom improvement and higher cerebral functions—mini-mental state examination (MMSE) and Frontal Assessment Battery (FAB) before and 12 months after shunting. LRG and tau protein concentrations in TT CSF were simultaneously measured using enzyme-linked immunosorbent assay. We then compared the predictive value of these concentrations with TT results regarding successful shunting outcomes.ResultsPositive combinations of TT and LRG concentrations of 67 ng/ml or higher, gave 81.6% sensitivity and 78.6% specificity. Therefore we used LRG (67 ng/ml) and tau (200 pg/ml) cut-off values, dividing patients into four groups. In group A (LRG ≥ 67 ng/ml and tau < 200 pg/ml) 31 of 34 patients (91.2%) had a positive TT and all operated 22 patients were shunt responders. Dementia MMSE and FAB scores in them increased from a baseline of 22.05(SE ± 0.96) to 25.65 (±0.85) and 11.38 (±0.68) to 13.08 (±0.57) respectively. In group B, (LRG ≥ 67 ng/ml and tau ≥ 200 pg/ml), the mean MMSE score increased from 17.62 (±2.03) to 21.62 (±1.96), and the FAB decreased slightly from 9.25 (±1.15) to 10.5 (±1.59), without improvement beyond the range of dementia. In group C, (LRG < 67 ng/ml, tau < 200 pg/ml), the mean MMSE score improved from 22.06 (±1.25) to 24.29 (±1.23) and the FAB score improved slightly from 12.0 (±0.72) to 12.87 (±0.72). Finally, in group D, (LRG < 67 ng/ml, tau ≥ 200 pg/ml), there was almost no improvement in MMSE scoreConclusionsA combination of positive TT and biomarkers quantification such as LRG and tau protein, can reliably predict shunting outcome in iNPH patients.

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“…No rise in CSF proteins in the first 24 h after death was reported by Mangin et al [43]. In contrast, Morihara et al [44] found a three-fold post-mortem increase with an average PMI of 5.7 h. A significant relationship with PMI was found for longer intervals [45]. Finehout et al [46] performed a proteomic analysis of both ante-and post-mortem CSF from seven individuals with short PMI (1.5-9.5 h) using two-dimensional gel electrophoresis (2DE) and mass spectrometry: 54 protein spots were identified, showing significantly different intensities between ante-and postmortem CSF.…”

Section: Hypoxanthinementioning

confidence: 83%

“…Morihara et al [44] showed that tau levels in demented and non-demented subjects were more than 30-fold higher in post-mortem CSF compared with those in antemortem CSF. Tau concentrations were also found to increase with PMI.…”

Section: Tau Proteinmentioning

confidence: 99%

Biochemical markers of time since death in cerebrospinal fluid: A first step towards“Forensomics”

Peyron

Lehmann

Delaby

et al. 2019

Critical Reviews in Clinical Laboratory Sciences

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Biochemical markers of time since death in cerebrospinal fluid: a first step towards "Forensomics" The accurate estimation of the time of death is a challenge in forensic medicine, as the methods routinely used to assess the post-mortem interval (PMI) are far from being precise. Over the past decades, biochemical methods have been implemented on post-mortem samples to improve the precision of PMI estimation. Studies have focussed on the biochemical profiles of closed compartment body fluids, as they are preserved longer than blood after death and are thus subject to confined post-mortem chemical changes. Cerebrospinal fluid (CSF) has been considered a suitable fluid to investigate these changes, as it is found in large amounts and is easy to sample. Moreover, the main molecules found in CSF have known reference values in living subjects, unlike most other body fluids. In this literature review, we focus on the panel of biomarkers that have been studied in CSF based on their potential of offering information on the time of death. The interest of these biomarkers in casework and the research perspectives in this field are discussed. Integrating data from different methods, including biochemistry, for better estimation of the time of death would represent a step forward in the forensic field, paving the way for an innovative approach that we suggest to call "Forensomics".

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Increased tau protein level in postmortem cerebrospinal fluid

Abstract: Key words postmortem cerebrospinal fluid

Cited by 18 publications

References 15 publications

Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on Aβ1-42 toxicity and uptake

Extracellular chaperones modulate the effects of Alzheimer’s patient cerebrospinal fluid on Aβ1-42 toxicity and uptake

Leucine-rich α-2-glycoprotein is a marker for idiopathic normal pressure hydrocephalus

Biochemical markers of time since death in cerebrospinal fluid: A first step towards“Forensomics”

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