Cerebrospinal Fluid Tau Levels in Neurodegenerative Diseases with Distinct Tau-Related Pathology

Arai, Hiroyuki; Morikawa, Yu Ichi; Higuchi, Makoto; Matsui, Toshifumi; Clark, Christopher M.; Miura, Masaru; Machida, Nobuo; Lee, Virginia M.‐Y.; Trojanowski, John Q.; Sasaki, Hidetada

doi:10.1006/bbrc.1997.6908

Cited by 146 publications

(81 citation statements)

References 14 publications

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“…DLB compared with PD, PDD, and AD showed the lowest CSF levels of Aβ42 and, when combined with CSF tau, differentiated DLB from PD and PDD; but not from AD [788], and PiB PET binding showed higher amyloid loaden in DLB and AD than in PD, PDD and controls [793,794]. While earlier studies showed increased CSF total (t)tau in both DLB and AD [795], others found differences for both t-tau and p-tau differentiating DLB from AD [796], and levels of t-tau and p-tau181 were significantly increased in DLB [797].…”

Section: α-Synuclein As a Biomarker For Synucleinopathiesmentioning

confidence: 75%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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Genetic, neuropathological and biochemical evidence implicates α-synuclein, a 140 amino acid presynaptic neuronal protein, in the pathogenesis of Parkinson's disease and other neurodegenerative disorders. The aggregated protein inclusions mainly containing aberrant α-synuclein are widely accepted as morphological hallmarks of α-synucleinopathies, but their composition and location vary between disorders along with neuronal networks affected. α-Synuclein exists physiologically in both soluble and membran-bound states, in unstructured and α-helical conformations, respectively, while posttranslational modifications due to proteostatic deficits are involved in β-pleated aggregation resulting in formation of typical inclusions. The physiological function of α-synuclein and its role linked to neurodegeneration, however, are incompletely understood. Soluble oligomeric, not fully fibrillar α-synuclein is thought to be neurotoxic, main targets might be the synapse, axons and glia. The effects of aberrant α-synuclein include alterations of calcium homeostasis, mitochondrial dysfunction, oxidative and nitric injuries, cytoskeletal effects, and neuroinflammation. Proteasomal dysfunction might be a common mechanism in the pathogenesis of neuronal degeneration in α-synucleinopathies. However, how α-synuclein induces neurodegeneration remains elusive as its physiological function. Genome wide association studies demonstrated the important role for genetic variants of the SNCA gene encoding α-synuclein in the etiology of Parkinson's disease, possibly through effects on oxidation, mitochondria, autophagy, and lysosomal function. The neuropathology of synucleinopathies and the role of α-synuclein as a potential biomarker are briefly summarized. Although animal models provided new insights into the pathogenesis of Parkinson disease and multiple system atrophy, most of them do not adequately reproduce the cardinal features of these disorders. Emerging evidence, in addition to synergistic interactions of α-synuclein with various pathogenic proteins, suggests that prionlike induction and seeding of α-synuclein could lead to the spread of the pathology and disease progression. Intervention in the early aggregation pathway, aberrant cellular effects, or secretion of α-synuclein might be targets for neuroprotection and disease-modifying therapy.

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Section: α-Synuclein As a Biomarker For Synucleinopathiesmentioning

confidence: 75%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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“…Furthermore, in patients with nonacute cerebrovascular disease without dementia, CSF T-tau is normal. 82,83 One way to interpret these findings is that a high CSF-tau level in a patient with clinical and brain imaging findings indicative of VAD suggests that this patient has mixed (AD/VAD) dementia.…”

Section: Csf T-taumentioning

confidence: 99%

“…Most studies have found normal to mildly increased CSF T-tau levels in other dementias, such as frontotemporal dementia (FTD) 14,15,21,50,52,69,70,73,[82][83][84][85][86] and Lewy body dementia (LBD). [85][86][87][88][89][90] Other than in aged nondemented individuals, normal CSF T-tau is found in depression, alcoholic dementia, and in chronic neurological disorders such as Parkinson's disease (PD) and progressive supranuclear palsy.…”

Section: Csf T-taumentioning

confidence: 99%

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

2004

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Summary:The introduction of acetylcholine esterase (AChE) inhibitors as a symptomatic treatment of Alzheimer's disease (AD) has made patients seek medical advice at an earlier stage of the disease. This has highlighted the importance of diagnostic markers for early AD. However, there is no clinical method to determine which of the patients with mild cognitive impairment (MCI) will progress to AD with dementia, and which have a benign form of MCI without progression. In this paper, the performance of cerebrospinal fluid (CSF) protein biomarkers for AD is reviewed. The diagnostic performance of the three biomarkers, total tau, phospho-tau, and the 42 amino acid form of ␤-amyloid have been evaluated in numerous studies and their ability to identify incipient AD in MCI cases has also been studied. Some candidate AD biomarkers including ubiquitin, neurofilament proteins, growth-associated protein 43 (neuromodulin), and neuronal thread protein (AD7c) show interesting results but have been less extensively studied. It is concluded that CSF biomarkers may have clinical utility in the differentiation between AD and several important differential diagnoses, including normal aging, depression, alcohol dementia, and Parkinson's disease, and also in the identification of Creutzfeldt-Jakob disease in cases with rapidly progressive dementia. Early diagnosis of AD is not only of importance to be able to initiate symptomatic treatment with AChE inhibitors, but will be the basis for initiation of treatment with drugs aimed at slowing down or arresting the degenerative process, such as ␥-secretase inhibitors, if these prove to affect AD pathology and to have a clinical effect.

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“…CSF tau level was shown to be significantly elevated in patients with AD compared with normal controls [76,77]. However, tau alone may lack diagnosis power since elevated CSF tau level has also been detected in patients with other neurodegenerative diseases [73,78]. The diagnostic yield may be improved by the simultaneous measurement of CSF Aβ42 and tau.…”

Section: Csf Aβ42 and Tau In Ad And Mild Cognitive Impairmentmentioning

confidence: 99%

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

Mao¹

2012

ABC

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Dementia is mainly a neurodegenerative disorder involved in several systems, including central nervous system, endocrinology/metabolism system and circulatory system. Alzheimer's disease (AD) and dementia with Lewy bodies (DLB) are the most common forms of the dementia, accounting for 60% -80% and 10% -20% of all cases, respectively. DLB is defined by widespread neocortical, limbic and brainstem Lewy bodies but frequently accompanied by variable levels of AD pathology. This pathological and clinical overlap makes their differential diagnosis complicated. Recent advances in the identification of disease biomarkers now make it possible to detect and distinguish their pathology in the early or preclinical stage of the diseases, even in cognitively normal individuals. In addition to the key biomarkers (amyloid β or Aβ, tau and α-synuclein), neurotrophins such as cocaineand amphetamine-regulated transcript (CART) have also drawn attention due to their expressions and functions. This article summarizes the progress in the definition, pathology and diagnosis of dementia, with a focus on potential biochemical markers in the cerebrospinal fluid (CSF) in the differential diagnosis of the main forms of dementia. To prediction or early diagnosis of dementia, the role of specific and sensitive CSF biomarkers seems to be crucial in a routine clinical setting. The concerns and challenges in the biomarker field are also discussed.

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Cerebrospinal Fluid Tau Levels in Neurodegenerative Diseases with Distinct Tau-Related Pathology

Cited by 146 publications

References 14 publications

The role of α-synuclein in neurodegeneration — An update

The role of α-synuclein in neurodegeneration — An update

Cerebrospinal fluid protein biomarkers for Alzheimer’s disease

Recent progress and concerns in dementia: Distinguishing Alzheimer's disease and dementia with Lewy bodies via biochemical markers in the cerebrospinal fluid

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