Differential levels of  -synuclein,  -amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease

Kasuga, Kensaku; Tokutake, Takayoshi; Ishikawa, Atsushi; Uchiyama, Tsuyoshi; Tokuda, Takahiko; Onodera, Osamu; Nishizawa, Masatoyo; Ikeuchi, Takeshi

doi:10.1136/jnnp.2009.197483

Cited by 140 publications

(100 citation statements)

References 17 publications

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“…Recent studies suggested that combinations of CSF measures may be able to differentiate DLB from other dementias: AS reduction in early DLB, a correlation between CSF-AS and Aβ42 measures (characteristic for DLB only), and total (t)-tau and p-tau 181, differentiating AD from DLB [798,799]. Combined analysis of CSF tau, Aβ42 and Aβ42/40 may differentiate between AD, DLB and PDD [800], while the differential association between amyloid precursor proteins sAPPα and sAPPβ with Aβ and tau species between DLB and AD suggests a relationship with their underlying pathologies [801].…”

Section: α-Synuclein As a Biomarker For Synucleinopathiesmentioning

confidence: 99%

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: 99%

The role of α-synuclein in neurodegeneration — An update

Jellinger¹

2012

Translational Neuroscience

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“…Mixed dementia may be more aggressive than pure AD (Kraybill, Larson et al 2005). Since a low CSF -Syn level was detected in CSF of patients with DLB and Parkinson disease comparing to other neurodegenerative diseases, an association of this measurement with typical CSF biomarkers of AD seems interesting (Tokuda, Salem et al 2006;Kasuga, Tokutake et al 2010). Moreover, oligomeric forms of -Syn were detected in CSF and blood of patients with Parkinson disease (El-Agnaf, .…”

Section: Which Techniques Could Be Applied?mentioning

confidence: 99%

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Elmoualij¹,

Dupiereux-Fettweis²,

Seguin³

et al. 2011

The Clinical Spectrum of Alzheimer's Disease -the Charge Toward Comprehensive Diagnostic and Therapeutic Strategies

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“…Furthermore, it has not been possible to use total CSF ␣-syn levels measured via immunoassay-based methods to distinguish between different synucleinopathies and other neurodegenerative disorders. Kasuga and colleagues reported significantly lower ␣-syn levels in the CSF of diffuse Lewy body disease patients than in patients with AD and other dementias (38), whereas others have found no significant differences between CSF ␣-syn levels when comparing diffuse Lewy body disease to other disorders (39,40).…”

mentioning

confidence: 95%

Alpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies

Schmid

Fauvet

Moniatte

et al. 2013

Molecular & Cellular Proteomics

159

120

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The development of novel therapies against neurodegenerative disorders requires the ability to detect their early, presymptomatic manifestations in order to enable treatment before irreversible cellular damage occurs. Precocious signs indicative of neurodegeneration include characteristic changes in certain protein levels, which can be used as diagnostic biomarkers when they can be detected in fluids such as blood plasma or cerebrospinal fluid. In the case of synucleinopathies, cerebrospinal alpha-synuclein (␣-syn) has attracted great interest as a potential biomarker; however, there is ongoing debate regarding the association between cerebrospinal ␣-syn levels and neurodegeneration in Parkinson disease and synucleinopathies. Post-translational modifications (PTMs) have emerged as important determinants of ␣-syn's physiological and pathological functions. Several PTMs are enriched within Lewy bodies and exist at higher levels in ␣-synucleinopathy brains, suggesting that certain modified forms of ␣-syn might be more relevant biomarkers than the total ␣-syn levels. However, the quantification of PTMs in bodily fluids poses several challenges. This review describes the limitations of current immunoassay-based ␣-syn quantification methods and highlights how these limitations can be overcome using novel mass-spectrometrybased assays. In addition, we describe how advances in chemical synthesis, which have enabled the preparation of ␣-syn proteins that are site-specifically modified at single or multiple residues, can facilitate the development of more accurate assays for detecting and quantifying ␣-syn PTMs in health and disease. Molecular & Cellular Proteomics

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Differential levels of -synuclein, -amyloid42 and tau in CSF between patients with dementia with Lewy bodies and Alzheimer's disease

Cited by 140 publications

References 17 publications

The role of α-synuclein in neurodegeneration — An update

The role of α-synuclein in neurodegeneration — An update

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

Alpha-synuclein Post-translational Modifications as Potential Biomarkers for Parkinson Disease and Other Synucleinopathies

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