Differential role of CSF alpha-synuclein species, tau, and Aβ42 in Parkinson's Disease (original) (raw)
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JAMA Neurol, 2013
IMPORTANCE We observed a significant correlation between cerebrospinal fluid (CSF) levels of tau proteins and α-synuclein, but not β-amyloid 1-42 (Aβ1-42), and lower concentration of CSF biomarkers, as compared with healthy controls, in a cohort of entirely untreated patients with Parkinson disease (PD) at the earliest stage of the disease studied so far. OBJECTIVE To evaluate the baseline characteristics and relationship to clinical features of CSF biomarkers (Aβ1-42, total tau [T-tau], tau phosphorylated at threonine 181 [P-tau 181 ], and α-synuclein) in drug-naive patients with early PD and demographically matched healthy controls enrolled in the Parkinson's Progression Markers Initiative (PPMI) study.
Amyloid-β and α-synuclein cerebrospinal fluid biomarkers and cognition in early Parkinson's disease
Parkinsonism & related disorders, 2015
Cognitive impairment in early Parkinson's disease (PD) is common and distinct from early Alzheimer's disease. Predictors and mechanisms are only partially known, but α-synuclein, amyloid-β and tau dysmetabolism may be involved. Our aim was to study associations between cerebrospinal fluid biomarkers (CSF) and cognition in non-dementia PD compared to normal controls (NC) and non-PD patients with mild cognitive impairment (MCI non-PD). Patients were classified as having normal, subjective or mild cognitive impairment after cognitive screening. CSF levels of total α-synuclein (t-α-syn), amyloid-β (Aβ) 38, 40 and 42, total tau (T-tau) and phosphorylated tau (P-tau) were measured in 34 NC, 31 early, non-dementia PD and 28 MCI non-PD patients. A well validated neuropsychological test battery was administered. In the PD group, 13 had normal cognition, 4 had subjective and 14 mild cognitive impairment. PD patients had significantly lower CSF biomarker levels of t-α-syn, Aβ38, 40 and...
CSF Aβ 42 and tau in Parkinson's disease with cognitive impairment
Movement Disorders, 2010
We tested the hypothesis that the CSF biomarker signature associated with Alzheimer's disease (AD) is present in a subset of individuals with Parkinson's disease and Dementia (PD-D) or with PD and Cognitive Impairment, Not Dementia (PD-CIND). We quantified CSF Aβ 42 , total tau (Ttau), and phospho-tau (P181-Tau) using commercially available kits. Samples were from 345 individuals in seven groups (n): Controls ≤ 50 years (35), Controls > 50 years (115), amnestic Mild Cognitive Impairment (aMCI) (24), AD (49), PD (49), PD-CIND (62), and PD-D (11). We observed expected changes in AD or aMCI compared with age-matched or younger controls. CSF Aβ 42 was reduced in PD-CIND (P < 0.05) and PD-D (P < 0.01) while average CSF T-Tau and P181-Tau were unchanged or decreased. One-third of PD-CIND and one-half of PD-D patients had the biomarker signature of AD. Abnormal metabolism of Aβ 42 may be a common feature of PD-CIND and PD-D.
Advances in Clinical and Experimental Medicine, 2020
Background. Parkinson's disease (PD) is a progressive neurodegenerative disorder with a characteristic clinical picture. Apart from classical movement disorders, a significant role is also played by non-motor symptoms, in particular cognitive impairments, which have a significant impact on the quality of life of the patients. Tau protein and amyloid beta are well-known non-specific biomarkers in Alzheimer's disease (AD). Objectives. The study assessed the practical value of determining tau protein and amyloid beta (Aβ42) in the blood serum of patients with PD and their relationship with cognitive impairments, radiographic image and the used dose of L-DOPA. Material and methods. The neuropsychological assessment was carried for 64 patients with PD. The levels of amyloid beta 1-42 (Aβ42) and tau proteins in serum were also measured. Results. The Aβ42 level in the serum was statistically higher in patients with longer duration of the disease (p < 0.05) and those who were taking a higher dose of L-DOPA (p < 0.05). The average level of tau protein in the serum was slightly lower in the study groups than in the control group and showed no statistical significance. No correlation was found between the levels of tau protein and Aβ42 and the results of neuropsychological tests. Tau protein correlated with hippocampal atrophy (p < 0.05). Conclusions. Serum levels of Aβ42 and tau protein in PD may be a useful marker for the assessment of cognitive impairments. The role of L-DOPA in the process of dementia in PD remains unclear.
Open Access Macedonian Journal of Medical Sciences, 2022
BACKGROUND: Most people with Parkinson's disease will develop dementia, along with their illness development. There are several overlapping brain pathological features in patients with Parkinson's and Alzheimer's disease. These features are related to beta-amyloid findings, alpha-synuclein, and tau protein. AIM: This study was designed to determine the relationship between beta-amyloid, alpha-synuclein, and tau protein plasma level with cognitive impairment in Parkinson's disease. MATERIALS AND METHODS: This was observational with case-control design study. A total of 62 patients with Parkinson's disease and 20 healthy controls were included in this study. Parkinson's disease group was divided into two subgroups, patients with and without cognitive impairment based on Montreal Cognitive Assessment Indonesian version (MoCA-Ina) score. The plasma levels of beta-amyloid, alpha-synuclein, and tau protein were measured using the enzyme-linked immunoassay technique. Student's t-test was used to analyze normally distributed data of plasma level differences between groups (Parkinson's disease group; control group) and subgroups (Parkinson disease with and without cognitive impairment). If the data were not normally distributed, the Mann-Whitney U-test was used. The level of significance was < 0.05 (p < 0.05). RESULTS: The result demonstrated significant differences in beta-amyloid, alpha-synuclein, and tau protein plasma level between Parkinson's disease and control group (p < 0.05). We also found significant differences of betaamyloid plasma level between Parkinson's with and without cognitive impairment subgroups (p < 0.05), but none in other parameters (p > 0.05). CONCLUSION: Low plasma levels of beta-amyloid 42 (Aβ42) are associated with cognitive impairment in patients with Parkinson's disease.
Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson's disease and degenerative dementias
Movement Disorders, 2011
A B S T R A C T : Although alpha-synuclein is the main constituent of Lewy bodies, cerebrospinal fluid determination on its own does not seem fundamental for the diagnosis of synucleinopathies. We evaluated whether the combination of classical biomarkers, Ab 1-42 , total tau, phosphorylated tau, and a-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. Ab 1-42 , total tau, phosphorylated tau, and a-synuclein were measured in a series of patients with Parkinson's disease (n ¼ 38), dementia with Lewy bodies (n ¼ 32), Alzheimer's disease (n ¼ 48), frontotemporal dementia (n ¼ 31), and age-matched control patients with other neurological diseases (n ¼ 32). Mean asynuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of a-synuclein with total tau (r ¼ À0.196, P <.01) was observed. In the group of patients with Parkinson's disease, Ab 1-42 , total tau, and phosphorylated tau values were similar to controls, whereas total tau/a-synu-clein and phosphorylated tau/a-synuclein ratios showed the lowest values. Cerebrospinal fluid a-synuclein alone did not provide relevant information for Parkinson's disease diagnosis, showing low specificity (area under the curve, 0.662; sensitivity, 94%; specificity, 25%). Instead, a better performance was obtained with the total tau/a-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of a-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/a-synuclein and phosphorylated tau/a-synuclein ratios can contribute to the discrimination of Parkinson's disease. V C 2011 Movement Disorder Society
Journal of Neurology, Neurosurgery & Psychiatry
ObjectiveTo evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson’s disease (PD).MethodsProspective, longitudinal, observational study up to 10 years with follow-up every 2 years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men).ResultsPatients with PD with low CSF Aβ1–42 levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ1–42 levels. Sixty-seven per cent of the patients with low Aβ1–42 levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ1–42 levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ1–42 levels at baseline developed cognitive impairment more frequently and earlier during follow-up.Concl...
Background: The Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers Aβ 1–42 , t-tau, and p-tau 181 overlap with other diseases. New tau modifications or epitopes, such as the non-phosphorylated tau fraction (p-tau rel), may improve differential dementia diagnosis. The goal of this study is to investigate if p-tau rel can improve the diagnostic performance of the AD CSF biomarker panel for differential dementia diagnosis. Methods: The study population consisted of 45 AD, 45 frontotemporal lobar degeneration (FTLD), 45 dementia with Lewy bodies (DLB), and 21 Creutzfeldt-Jakob disease (CJD) patients, and 20 cognitively healthy controls. A substantial subset of the patients was pathology-confirmed. CSF levels of Aβ 1–42 , t-tau, p-tau 181 , and p-tau rel were determined with commercially available single-analyte enzyme-linked immunosorbent assay (ELISA) kits. Diagnostic performance was evaluated by receiver operating characteristic (ROC) curve analyses, and area under the curve (AUC) values were compared using DeLong tests. Results: The diagnostic performance of single markers as well as biomarker ratios was determined for each pairwise comparison of different dementia groups and controls. The addition of p-tau rel to the AD biomarker panel decreased its diagnostic performance when discriminating non-AD, FTLD, and DLB from AD. As a single marker, p-tau rel increased the diagnostic performance for CJD. No significant difference was found in AUC values with the addition of p-tau rel when differentiating between AD or non-AD dementias and controls. Conclusions: The addition of p-tau rel to the AD CSF biomarker panel failed to improve differentiation between AD and non-AD dementias.
A single center study: Aβ42/p-Tau181 CSF ratio to discriminate AD from FTD in clinical setting
Neurological Sciences, 2017
Abnormal levels of beta amyloid (Aβ42) and tau protein concentrations in the cerebral spinal fluid (CSF) have been largely described in Alzheimer's disease (AD). Thus, CSF analysis of these biomarkers has been incorporated in recent AD diagnostic criteria, and it is increasingly performed for neurodegenerative dementia diagnostic workout in clinical setting. Nevertheless, the precise biomarkers CSF features in neurodegenerative dementia, either AD or Frontotemporal dementia (FTD), are still not fully clear today. This is mainly due to lack of CSF clear cutoff values due to a well-known intersite (but even intrasite) variability of CSF procedures, ranging from collection to analysis. Applying CSF biomarker ratios, rather than their single values could represent a useful tool, especially for the differential diagnosis of different forms of dementia. We explored clinical values of six CSF ratios (by combining Aβ42 and tau) in order to better discriminate between AD and FTD; we identified Aβ42/p-Tau 181 ratio as a potential good candidate for helping differentiating AD from FTD in the clinical practice.