Cerebrospinal fluid Tau/α-synuclein ratio in Parkinson's disease and degenerative dementias.

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, Aβ(1-42) , total tau, phosphorylated tau, and α-synuclein can improve discrimination of Parkinson's disease, dementia with Lewy bodies, Alzheimer's disease, and frontotemporal dementia. Aβ(1-42) , total tau, phosphorylated tau, and α-synuclein were measured in a series of patients with Parkinson's disease (n = 38), dementia with Lewy bodies (n = 32), Alzheimer's disease (n = 48), frontotemporal dementia (n = 31), and age-matched control patients with other neurological diseases (n = 32). Mean α-synuclein levels in cerebrospinal fluid were significantly lower in the pathological groups than in cognitively healthy subjects. An inverse correlation of α-synuclein with total tau (r = -0.196, P < .01) was observed. In the group of patients with Parkinson's disease, Aβ(1-42) , total tau, and phosphorylated tau values were similar to controls, whereas total tau/α-synuclein and phosphorylated tau/α-synuclein ratios showed the lowest values. Cerebrospinal fluid α-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/α-syn ratio (area under the curve, 0.765; sensitivity, 89%; specificity, 61%). Combined determination of α-synuclein and classical biomarkers in cerebrospinal fluid shows differential patterns in neurodegenerative disorders. In particular, total tau/α-synuclein and phosphorylated tau/α-synuclein ratios can contribute to the discrimination of Parkinson's disease. © 2011 Movement Disorder Society.

Parnetti L ，Chiasserini D ，Bellomo G ，Giannandrea D ，De Carlo C ，Qureshi MM ，Ardah MT ，Varghese S ，Bonanni L ，Borroni B ，Tambasco N ，Eusebi P ，Rossi A ，Onofrj M ，Padovani A ，Calabresi P ，El-Agnaf O ... -  《-》

α-Synuclein and tau concentrations in cerebrospinal fluid of patients presenting with parkinsonism: a cohort study.

Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy are brain disorders characterised by intracellular α-synuclein deposits. We aimed to assess whether reduction of α-synuclein concentrations in CSF was a marker for α-synuclein deposition in the brain, and therefore diagnostic of synucleinopathies. We assessed potential extracellular-fluid markers of α-synuclein deposition in the brain (total α-synuclein and total tau in CSF, and total α-synuclein in serum) in three cohorts: a cross-sectional training cohort of people with Parkinson's disease, multiple system atrophy, dementia with Lewy bodies, Alzheimer's disease, or other neurological disorders; a group of patients with autopsy-confirmed dementia with Lewy bodies, Alzheimer's disease, or other neurological disorders (CSF specimens were drawn ante mortem during clinical investigations); and a validation cohort of patients who between January, 2003, and December, 2006, were referred to a specialised movement disorder hospital for routine inpatient admission under the working diagnosis of parkinsonism. CSF and serum samples were assessed by ELISA, and clinical diagnoses were made according to internationally established criteria. Mean differences in biomarkers between diagnostic groups were assessed with conventional parametric and non-parametric statistics. In our training set, people with Parkinson's disease, multiple system atrophy, and dementia with Lewy bodies had lower CSF α-synuclein concentrations than patients with Alzheimer's disease and other neurological disorders. CSF α-synuclein and tau values separated participants with synucleinopathies well from those with other disorders (p<0·0001; area under the receiver operating characteristic curve [AUC]=0·908). In the autopsy-confirmed cases, CSF α-synuclein discriminated between dementia with Lewy bodies and Alzheimer's disease (p=0·0190; AUC=0·687); in the validation cohort, CSF α-synuclein discriminated Parkinson's disease and dementia with Lewy bodies versus progressive supranuclear palsy, normal-pressure hydrocephalus, and other neurological disorders (p<0·0001; AUC=0·711). Other predictor variables tested in this cohort included CSF tau (p=0·0798), serum α-synuclein (p=0·0502), and age (p=0·0335). CSF α-synuclein concentrations of 1·6 pg/μL or lower showed 70·72% sensitivity (95% CI 65·3-76·1%) and 52·83% specificity (39·4-66·3%) for the diagnosis of Parkinson's disease. At this cutoff, the positive predictive value for any synucleinopathy was 90·7% (95% CI 87·3-94·2%) and the negative predictive value was 20·4% (13·7-27·2%). Mean CSF α-synuclein concentrations as measured by ELISA are significantly lower in Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy than in other neurological diseases. Although specificity was low, the high positive predictive value of CSF α-synuclein concentrations in patients presenting with synucleinopathy-type parkinsonism might be useful in stratification of patients in future clinical trials. American Parkinson Disease Association, Stifterverband für die Deutsche Wissenschaft, Michael J Fox Foundation for Parkinson's Research, National Institutes of Health, Parkinson Research Consortium Ottawa, and the Government of Canada.

Mollenhauer B ，Locascio JJ ，Schulz-Schaeffer W ，Sixel-Döring F ，Trenkwalder C ，Schlossmacher MG ... -  《-》

Cerebrospinal fluid tau and amyloid-β1-42 in patients with dementia.

Progressive cognitive decline in combination with a cerebrospinal fluid biomarker pattern of low levels of amyloid-β1-42 and high levels of total tau and phosphorylated tau is typical of Alzheimer's disease. However, several neurodegenerative disorders may overlap with Alzheimer's disease both in regards to clinical symptoms and neuropathology. In a uniquely large cohort of dementia patients, we examined the associations of cerebrospinal fluid biomarkers for Alzheimer's disease molecular pathology with clinical dementia diagnoses and disease severity. We cross-referenced the Swedish Dementia Registry with the clinical laboratory database at the Sahlgrenska University Hospital. The final data set consisted of 5676 unique subjects with a clinical dementia diagnosis and a complete set of measurements for cerebrospinal fluid amyloid-β1-42, total tau and phosphorylated tau. In cluster analysis, disregarding clinical diagnosis, the optimal natural separation of this data set was into two clusters, with the majority of patients with early onset Alzheimer's disease (75%) and late onset Alzheimer's disease (73%) assigned to one cluster and the patients with vascular dementia (91%), frontotemporal dementia (94%), Parkinson's disease dementia (94%) and dementia with Lewy bodies (87%) to the other cluster. Frontotemporal dementia had the highest cerebrospinal fluid levels of amyloid-β1-42 and the lowest levels of total tau and phosphorylated tau. The highest levels of total tau and phosphorylated tau and the lowest levels of amyloid-β1-42 and amyloid-β1-42:phosphorylated tau ratios were found in Alzheimer's disease. Low amyloid-β1-42, high total tau and high phosphorylated tau correlated with low Mini-Mental State Examination scores in Alzheimer's disease. In Parkinson's disease dementia and vascular dementia low cerebrospinal fluid amyloid-β1-42 was associated with low Mini-Mental State Examination score. In the vascular dementia, frontotemporal dementia, dementia with Lewy bodies and Parkinson's disease dementia groups 53%, 34%, 67% and 53% of the subjects, respectively had abnormal amyloid-β1-42 levels, 41%, 41%, 28% and 28% had abnormal total tau levels, and 29%, 28%, 25% and 19% had abnormal phosphorylated tau levels. Cerebrospinal fluid biomarkers were strongly associated with specific clinical dementia diagnoses with Alzheimer's disease and frontotemporal dementia showing the greatest difference in biomarker levels. In addition, cerebrospinal fluid amyloid-β1-42, total tau, phosphorylated tau and the amyloid-β1-42:phosphorylated tau ratio all correlated with poor cognitive performance in Alzheimer's disease, as did cerebrospinal fluid amyloid-β1-42 in Parkinson's disease dementia and vascular dementia. The results support the use of cerebrospinal fluid biomarkers to differentiate between dementias in clinical practice, and to estimate disease severity.

Skillbäck T ，Farahmand BY ，Rosén C ，Mattsson N ，Nägga K ，Kilander L ，Religa D ，Wimo A ，Winblad B ，Schott JM ，Blennow K ，Eriksdotter M ，Zetterberg H ... -  《-》

Accuracy of a panel of 5 cerebrospinal fluid biomarkers in the differential diagnosis of patients with dementia and/or parkinsonian disorders.

Hall S ，Öhrfelt A ，Constantinescu R ，Andreasson U ，Surova Y ，Bostrom F ，Nilsson C ，Håkan W ，Decraemer H ，Någga K ，Minthon L ，Londos E ，Vanmechelen E ，Holmberg B ，Zetterberg H ，Blennow K ，Hansson O ... -  《-》

Cerebrospinal fluid biomarkers in Parkinson's disease with dementia and dementia with Lewy bodies.

Parnetti L ，Tiraboschi P ，Lanari A ，Peducci M ，Padiglioni C ，D'Amore C ，Pierguidi L ，Tambasco N ，Rossi A ，Calabresi P ... -  《-》