CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation

Shim, Kyu Hwan; Kang, Min Ju; Suh, Jung Won; Pyun, Jung Min; Ryoo, Nayoung; Park, Young Ho; Youn, Young Chul; Jang, Jae Won; Jeong, Jee Hyang; Park, Kyung Won; Choi, Seong Hye; Suk, Kyoungho; Lee, Ho Won; Ko, Pan Woo; Lee, Chan Nyoung; Lim, Tae Sung; An, Seong Soo A.; Kim, SangYun

doi:10.1186/s13195-020-00648-9

Cited by 16 publications

(27 citation statements)

References 39 publications

(54 reference statements)

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“…In our previous publication [ 19 ], we found that diagnosis validity was high for both α-syn and p-tau 181p , and their combination improved the discrimination of MCI-AD from the other three groups. For that reason, we and others [ 9 ] consider that combined measurements could provide a pathophysiological report that would be highly important for the new concept of “precision medicine” in degenerative dementia [ 24 ].…”

Section: Discussionmentioning

confidence: 99%

“…Quantification of α-syn protein in the CSF of AD patients is not usual practice. However, it has been studied by different authors [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 ]. Most of the published results indicate that CSF α-syn, in combination with the “core” AD CSF biomarkers, have clinical value in the differential diagnosis of AD and LBD at the stage of dementia, but few authors have not found a role for CSF α-syn as a useful biomarker for AD [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

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Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease

et al. 2021

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Background: Alzheimer’s disease (AD) is characterized by the presence of β-amyloid plaques and neurofibrillary tangles, while Lewy body dementia (LBD) is characterized by α-synuclein (α-syn) inclusions. Some authors examine α-syn protein in the neurodegeneration process of AD and propose to consider cerebrospinal fluid (CSF) α-syn as a possible additional biomarker to the so-called “core” of AD. Objective: To determine whether there is a correlation between α-syn levels and “core” AD biomarkers in patients with mild cognitive impairment (MCI). Materials and methods: In total, 81 patients in the early stages of MCI were selected from the outpatient dementia consultation in Alicante General Hospital. Using a cross-sectional case–control design, patients were analyzed in four groups: stable MCI (MCIs; n = 25), MCI due to AD (MCI-AD; n = 32), MCI due to LBD (MCI-LBD; n = 24) and a control group of patients with acute or chronic headache (Ctrl; n = 18). Correlation between CSF protein levels in the different groups was assessed by the Rho Spearman test. Results: We found positive correlations between T-tau protein and α-syn (ρ = 0.418; p value < 0.05) and p-tau181p and α-syn (ρ = 0.571; p value < 0.05) exclusively in the MCI-AD group. Conclusion: The correlation found between α-syn and tau proteins in the first stages of AD support the involvement of α-syn in the pathogenesis of AD. This result may have clinical and diagnostic implications, as well as help to apply the new concept of “precision medicine” in patients with MCI.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease

et al. 2021

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“…Recent evidence suggests that α-, and also βand γ-synuclein, may be effective markers of AD rather than synucleinopathy [82]. Both αand β-synuclein may be early markers of AD, even in non-demented elder subjects [83,84], while the ratio of total tau/α-synuclein may serve as a marker of tau phosphorylation, even allowing patients with the A − T + (N + ) profile to re-enter the AD diagnostic group [85]. Blood-based classical [86,87] and exosomal [88] biomarkers may prove helpful, especially for frequent monitoring of the biochemical effects of anti-amyloid antibodies.…”

Section: Discussionmentioning

confidence: 99%

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

et al. 2021

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Analysis of classical cerebrospinal fluid biomarkers, especially when incorporated in a classification/diagnostic system such as the AT(N), may offer a significant diagnostic tool allowing correct identification of Alzheimer’s disease during life. We describe four patients with more or less atypical or mixed clinical presentation, in which the classical cerebrospinal fluid biomarkers amyloid peptide with 42 and 40 amino acids (Aβ42 and Aβ40, respectively), phospho-tau (τP-181) and total tau (τΤ) were measured. Despite the unusual clinical presentation, the biomarker profile was compatible with Alzheimer’s disease in all four patients. The measurement of classical biomarkers in the cerebrospinal fluid may be a useful tool in identifying the biochemical fingerprints of Alzheimer’s disease, especially currently, due to the recent approval of the first disease-modifying treatment, allowing not only typical but also atypical cases to be enrolled in trials of such treatments.

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“…Based on the central role of α-syn in PD pathogenesis, great attention has been paid to α-syn levels in CSF as a promising biomarker. Notably, the majority of studies consistently report lower CSF levels of total α-syn (t-α-syn) as compared to healthy controls [ 8 , 9 , 10 ], in contrast to the inconclusive findings in peripheral blood [ 11 , 12 , 13 ]. However, CSF t-α-syn levels vary greatly among studies, likely due to clinical heterogeneity and methodological differences that could compromise diagnostic accuracy.…”

Section: Alpha-synucleinmentioning

confidence: 99%

Update on CSF Biomarkers in Parkinson’s Disease

et al. 2022

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Progress in developing disease-modifying therapies in Parkinson’s disease (PD) can only be achieved through reliable objective markers that help to identify subjects at risk. This includes an early and accurate diagnosis as well as continuous monitoring of disease progression and therapy response. Although PD diagnosis still relies mainly on clinical features, encouragingly, advances in biomarker discovery have been made. The cerebrospinal fluid (CSF) is a biofluid of particular interest to study biomarkers since it is closest to the brain structures and therefore could serve as an ideal source to reflect ongoing pathologic processes. According to the key pathophysiological mechanisms, the CSF status of α-synuclein species, markers of amyloid and tau pathology, neurofilament light chain, lysosomal enzymes and markers of neuroinflammation provide promising preliminary results as candidate biomarkers. Untargeted approaches in the field of metabolomics provide insights into novel and interconnected biological pathways. Markers based on genetic forms of PD can contribute to identifying subgroups suitable for gene-targeted treatment strategies that might also be transferable to sporadic PD. Further validation analyses in large PD cohort studies will identify the CSF biomarker or biomarker combinations with the best value for clinical and research purposes.

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CSF total tau/α-synuclein ratio improved the diagnostic performance for Alzheimer’s disease as an indicator of tau phosphorylation

Cited by 16 publications

References 39 publications

Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease

Relation between Alpha-Synuclein and Core CSF Biomarkers of Alzheimer’s Disease

From Cerebrospinal Fluid Neurochemistry to Clinical Diagnosis of Alzheimer’s Disease in the Era of Anti-Amyloid Treatments. Report of Four Patients

Update on CSF Biomarkers in Parkinson’s Disease

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