Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity

Sämgård, Kajsa; Zetterberg, Henrik; Blennow, Kaj; Hansson, Oskar; Minthon, Lennart; Londos, Elisabet

doi:10.1002/gps.2353

Cited by 114 publications

(82 citation statements)

References 46 publications

(43 reference statements)

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“…First, the ventricular CSF tau in this study was lower than spinal CSF tau measured from live patients (33)(34)(35). This difference might be attributable to different ELISA kits, heterogeneous patient populations or anatomic sources of CSF.…”

Section: à6mentioning

confidence: 64%

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Han

Serrano

Beach

et al. 2017

J Neuropathol Exp Neurol

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Neurofibrillary tangles (NFTs) represent products of insoluble tau protein in the brains of patients with Alzheimer disease (AD). The cerebrospinal fluid (CSF) tau level is a biomarker in AD diagnosis. The soluble portion of tau protein in brain parenchyma is presumably the source for CSF tau but this has not previously been quantified. We measured CSF tau and soluble brain tau at autopsy in temporal and frontal brain tissue samples from 7 cognitive normal, 12 mild cognitively impaired, and 19 AD subjects. Based on the measured brain soluble tau, we calculated the whole brain tau load and estimated tau secretion factor. Our results suggest that the increase in NFT in AD is likely attributable to post-translational processes; the increase in CSF tau in AD patients is due to an accelerated carrier-based secretion. Moreover, cognitive dysfunction assessed by final Mini-Mental State Examination scores correlated with the secretion factor but not with the soluble tau.

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Section: à6mentioning

confidence: 64%

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Han

Serrano

Beach

et al. 2017

J Neuropathol Exp Neurol

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“…The degree of increase in CSF T-tau in chronic neurodegenerative disorders is highest in disorders with the most rapid neuronal degeneration, such as Creutzfeldt-Jakob disease (Otto et al 1997). High CSF T-tau is also associated with a faster progression from mild cognitive impairment (MCI) to AD (Blom et al 2009), and a more rapid cognitive decline and higher mortality in AD cases (Samgard et al 2009;Wallin et al 2009). However, one study found that CSF Ttau correlates with postmortem tangle load (Tapiola et al 2009), suggesting that the release of tau specifically from degenerating tanglebearing neurons may contribute to the CSF level of T-tau.…”

Section: Fluid Biomarkers and The Brainmentioning

confidence: 99%

“…Positive correlations between CSF levels of P-tau 181 and P-tau 231 (tau phosphorylated at residues 181 and 231, respectively) and neocortical tangle pathology at autopsy have been reported (Buerger et al 2006;Tapiola et al 2009). High CSF P-tau181 is also associated with a faster progression from MCI to AD (Blom et al 2009), and a more rapid cognitive decline in AD cases (Samgard et al 2009), as well as those with very mild AD dementia (Snider et al 2009). These findings support the hypothesis that the CSF level of P-tau reflects the phosphorylation state of tau and the formation of tangles in the brain.…”

Section: Fluid Biomarkers and The Brainmentioning

confidence: 99%

Fluid Biomarkers in Alzheimer Disease

Blennow

Zetterberg

Fagan

2012

Cold Spring Harbor Perspectives in Medicine

171

148

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Research progress has provided detailed understanding of the molecular pathogenesis of Alzheimer disease (AD). This knowledge has been translated into new drug candidates with putative disease-modifying effects, which are now being tested in clinical trials. The promise of effective therapy has created a great need for biomarkers able to detect AD in the predementia phase, because drugs will probably be effective only if neurodegeneration is not too advanced. In this chapter, cerebrospinal fluid (CSF) and plasma biomarkers are reviewed. The core CSF biomarkers total tau (T-tau), phosphorylated tau (P-tau) and the 42 amino acid form of b-amyloid (Ab42) reflect AD pathology, and have high diagnostic accuracy to diagnose AD with dementia and prodromal AD in mild cognitive impairment cases. The rationale for the use of CSF biomarkers to identify and monitor the mechanism of action of new drug candidates is also outlined in this chapter.

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“…Its levels increase in Creutzfeld-Jakob disease, and it may also be found in dementia associated with VCI, cerebral trauma and AD [157][158][159]. The usefulness of tau protein in the diagnosis of vascular dementia is to exclude other etiologies, so that there are no cut-off points for the diagnosis of vascular pathology [160].…”

Section: Genetic and Inflammatory Biomarkers And Their Neuropathologimentioning

confidence: 99%

“…There is usually an elevation of this ratio in patients with vascular dementia (particularly due to subcortical vessel disease) [156,159,164].…”

Section: Csf and Serum Albumin Concentration Indexmentioning

confidence: 99%

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

Alvarado¹,

Brito²,

Román³

et al. 2017

J Neurol Neurosci

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Cerebral vascular disease (CVD) represents the second cause in years of life lost, according to the Global Burden of Disease Study 2015 study. The global report on Alzheimer's disease 2015 estimates that in Latin America there are 9.2 million cases of dementia, with a prevalence of 8.2%. Undoubtedly, Alzheimer's disease is the most frequent cause, followed by vascular dementia (VD) with 15% of the cases, although global data are unknown in Latin America. Objective:To analyze and present the current evidence on the classification, pathophysiology, diagnosis and treatment of vascular cognitive impairment. Methodology:A group of experts met in Miami, Florida, in April 2016. The group included Neurologists, Geriatricians and Psychiatrists from the following countries: Mexico, Guatemala, El Salvador, Costa Rica, Peru, Spain, Bolivia, Chile, Paraguay, Colombia, Panama, Venezuela, Italy, the United States, Dominican Republic, Honduras and Nicaragua. The Delphi method was used to review available information (provided months before the meeting), in relation to assigned topics: definition of Cognitive Vascular Impairment (CVI), risk factors, pathophysiology, diagnosis (neuropsychological and imaging) and treatment. For the allocation of evidence and recommendation of available treatments, the GRADE system was used.The working groups analyzed and discussed available evidence on CVI concerning proposed definitions, risk factors and diagnostic elements. Subsequently, the conclusions of each of the working groups were drafted, which were reviewed by each of the authors and by the rest of the study groups until a global consensus was reached. Once this process was completed, the process of external validation and preparation of the final document was carried out.The results of this consensus allow the incorporation of the opinion and experience of physicians of different specialties in Latin America regarding the vascular cognitive impairment.

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Cerebrospinal fluid total tau as a marker of Alzheimer's disease intensity

Abstract: These findings support the hypothesis that increased levels of T-tau reflect the intensity of the disease and are associated with a more rapid disease progress.

Cited by 114 publications

References 46 publications

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

A Quantitative Analysis of Brain Soluble Tau and the Tau Secretion Factor

Fluid Biomarkers in Alzheimer Disease

Latin American Delphi Consensus on Vascular Cognitive Impairment: Definitions, Clinical Features, Pathophysiology, Prevention and Treatment

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