Dataset Information

CSF ?-synuclein improves diagnostic and prognostic performance of CSF tau and A? in Alzheimer's disease.

ABSTRACT: Alzheimer's disease (AD) and Lewy body diseases (LBD), e.g., Parkinson's disease (PD) dementia and dementia with Lewy bodies (DLB), are common causes of geriatric cognitive impairments. In addition, AD and LBD are often found in the same patients at autopsy; therefore, biomarkers that can detect the presence of both pathologies in living subjects are needed. In this investigation, we report the assessment of ?-synuclein (?-syn) in cerebrospinal fluid (CSF) and its association with CSF total tau (t-tau), phosphorylated tau181 (p-tau181), and amyloid beta1-42 (A?1-42) in subjects of the Alzheimer's Disease Neuroimaging Initiative (ADNI; n = 389), with longitudinal clinical assessments. A strong correlation was noted between ?-syn and t-tau in controls, as well as in patients with AD and mild cognitive impairment (MCI). However, the correlation is not specific to subjects in the ADNI cohort, as it was also seen in PD patients and controls enrolled in the Parkinson's Progression Markers Initiative (PPMI; n = 102). A bimodal distribution of CSF ?-syn levels was observed in the ADNI cohort, with high levels of ?-syn in the subjects with abnormally increased t-tau values. Although a correlation was also noted between ?-syn and p-tau181, there was a mismatch (?-syn-p-tau181-Mis), i.e., higher p-tau181 levels accompanied by lower ?-syn levels in a subset of ADNI patients. We hypothesize that this ?-syn-p-tau181-Mis is a CSF signature of concomitant LBD pathology in AD patients. Hence, we suggest that inclusion of measures of CSF ?-syn and calculation of ?-syn-p-tau181-Mis improves the diagnostic sensitivity/specificity of classic CSF AD biomarkers and better predicts longitudinal cognitive changes.

SUBMITTER: Toledo JB

PROVIDER: S-EPMC3812407 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer's disease.

Toledo Jon B JB Korff Ane A Shaw Leslie M LM Trojanowski John Q JQ Zhang Jing J

Acta neuropathologica 20130629 5

Alzheimer's disease (AD) and Lewy body diseases (LBD), e.g., Parkinson's disease (PD) dementia and dementia with Lewy bodies (DLB), are common causes of geriatric cognitive impairments. In addition, AD and LBD are often found in the same patients at autopsy; therefore, biomarkers that can detect the presence of both pathologies in living subjects are needed. In this investigation, we report the assessment of α-synuclein (α-syn) in cerebrospinal fluid (CSF) and its association with CSF total tau ...[more]

PMID: 23812319

Similar Datasets

Project description:BackgroundRecently, several studies suggested potential involvements of α-synuclein in Alzheimer's disease (AD) pathophysiology. Higher concentrations of α-synuclein were reported in cerebrospinal fluid (CSF) of AD patients with a positive correlation towards CSF tau, indicating its possible role in AD. We analyzed the CSF biomarkers to verify whether α-synuclein could be an additional supported biomarker in AD diagnosis.MethodsIn this cross-sectional study, CSF samples of 71 early-onset AD, 34 late-onset AD, 11 mild cognitive impairment, 17 subjective cognitive decline, 45 Parkinson's disease, and 32 healthy control (HC) were collected. CSF amyloid-β1-42 (A), total tau (N), and phosphorylated tau181 (T) were measured by commercial ELISA kits, and in-house ELISA kit was developed to quantify α-synuclein. The cognitive assessments and amyloid-PET imaging were also performed.ResultsCSF α-synuclein manifested a tendency to increase in AD and to decreased in Parkinson's disease compared to HC. The equilibrium states of total tau and α-synuclein concentrations were changed significantly in AD, and the ratio of total tau/α-synuclein (N/αS) was dramatically increased in AD than HC. Remarkably, N/αS revealed a strong positive correlation with tau phosphorylation rate. Also, the combination of N/αS with amyloid-β1-42/phosphorylated tau181 ratio had the best diagnosis performance (AUC = 0.956, sensitivity = 96%, specificity = 87%). In concordance analysis, N/αS showed the higher diagnostic agreement with amyloid-β1-42 and amyloid-PET. Analysis of biomarker profiling with N/αS had distinctive characteristics and clustering of each group. Especially, among the group of suspected non-Alzheimer's disease pathophysiology, all A-T+N+ patients with N/αS+ were reintegrated into AD.ConclusionsThe high correlation of α-synuclein with tau and the elevated N/αS in AD supported the involvement of α-synuclein in AD pathophysiology. Importantly, N/αS improved the diagnostic performance, confirming the needs of incorporating α-synuclein as a biomarker for neurodegenerative disorders. The incorporation of a biomarker group [N/αS] could contribute to provide better understanding and diagnosis of neurodegenerative disorders.

Dataset Information

CSF ?-synuclein improves diagnostic and prognostic performance of CSF tau and A? in Alzheimer's disease.

Publications

CSF α-synuclein improves diagnostic and prognostic performance of CSF tau and Aβ in Alzheimer's disease.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets