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 ... -  《-》

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 ... -  《-》

Assessment of cerebrospinal fluid (CSF) beta-amyloid (1-42), phosphorylated tau (ptau-181) and total Tau protein in patients with Alzheimer's disease (AD) and other dementia at Siriraj Hospital, Thailand.

Thaweepoksomboon J ，Senanarong V ，Poungvarin N ，Chakorn T ，Siwasariyanon N ，Washirutmangkur L ，Udompunthuruk S ... -  《-》

Alzheimer's disease cerebrospinal fluid biomarker in cognitively normal subjects.

In a large multicentre sample of cognitively normal subjects, as a function of age, gender and APOE genotype, we studied the frequency of abnormal cerebrospinal fluid levels of Alzheimer's disease biomarkers including: total tau, phosphorylated tau and amyloid-β1-42. Fifteen cohorts from 12 different centres with either enzyme-linked immunosorbent assays or Luminex® measurements were selected for this study. Each centre sent nine new cerebrospinal fluid aliquots that were used to measure total tau, phosphorylated tau and amyloid-β1-42 in the Gothenburg laboratory. Seven centres showed a high correlation with the new Gothenburg measurements; therefore, 10 cohorts from these centres are included in the analyses here (1233 healthy control subjects, 40-84 years old). Amyloid-β amyloid status (negative or positive) and neurodegeneration status (negative or positive) was established based on the pathological cerebrospinal fluid Alzheimer's disease cut-off values for cerebrospinal fluid amyloid-β1-42 and total tau, respectively. While gender did not affect these biomarker values, APOE genotype modified the age-associated changes in cerebrospinal fluid biomarkers such that APOE ε4 carriers showed stronger age-related changes in cerebrospinal fluid phosphorylated tau, total tau and amyloid-β1-42 values and APOE ε2 carriers showed the opposite effect. At 40 years of age, 76% of the subjects were classified as amyloid negative, neurodegeneration negative and their frequency decreased to 32% at 85 years. The amyloid-positive neurodegeneration-negative group remained stable. The amyloid-negative neurodegeneration-positive group frequency increased slowly from 1% at 44 years to 16% at 85 years, but its frequency was not affected by APOE genotype. The amyloid-positive neurodegeneration-positive frequency increased from 1% at 53 years to 28% at 85 years. Abnormally low cerebrospinal fluid amyloid-β1-42 levels were already frequent in midlife and APOE genotype strongly affects the levels of cerebrospinal fluid amyloid-β1-42, phosphorylated tau and total tau across the lifespan without influencing the frequency of subjects with suspected non-amyloid pathology.

Toledo JB ，Zetterberg H ，van Harten AC ，Glodzik L ，Martinez-Lage P ，Bocchio-Chiavetto L ，Rami L ，Hansson O ，Sperling R ，Engelborghs S ，Osorio RS ，Vanderstichele H ，Vandijck M ，Hampel H ，Teipl S ，Moghekar A ，Albert M ，Hu WT ，Monge Argilés JA ，Gorostidi A ，Teunissen CE ，De Deyn PP ，Hyman BT ，Molinuevo JL ，Frisoni GB ，Linazasoro G ，de Leon MJ ，van der Flier WM ，Scheltens P ，Blennow K ，Shaw LM ，Trojanowski JQ ，Alzheimer’s Disease Neuroimaging Initiative ... -  《-》

Comparisons of clinical symptoms in biomarker-confirmed Alzheimer's disease, dementia with Lewy bodies, and frontotemporal dementia patients in a local memory clinic.

There has been no previous Chinese study that differentiated the clinical symptoms among biomarker-confirmed Alzheimer's disease (AD), dementia with Lewy bodies (DLB) and frontotemporal dementia (FTD). The objective of this study was to compare the cognitive, behavioural, and neuropsychiatric symptoms in biomarker-confirmed AD, DLB, and FTD patients. We recruited 30 patients (14 AD, 7 DLB, 9 FTD) who presented to the memory clinic at Queen Mary Hospital from 1 January 2007 to 31 December 2013. AD was diagnosed according to the National Institution of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association criteria with cerebrospinal fluid biomarkers (tau, phosphorylated tau, and amyloid β-42) fulfilling locally determined cut-off values for AD. DLB was diagnosed based on the McKeith diagnostic criteria. The behavioural variant of FTD was diagnosed based on the revised diagnostic criteria proposed by the International bvFTD Criteria Consortium, and language variant FTD was diagnosed based on the latest published criteria. In addition, patients with DLB and FTD had typical imaging features on single-photon emission computed tomography or (18) fludeoxyglucose-positron emission tomography, either with or without Pittsburgh Compound B imaging, which supported their diagnoses. Data on patient characteristics including demographics, presenting clinical features, Mini-Mental State Examination, clinical dementia ratings, and neuropsychiatry inventory scores were collected. There were no differences in age, education level, dementia severity, and duration of symptoms before presentation among the three subgroups of patients. All patients had amnesia symptoms, which were not statistically significant. Apraxia was most common in AD. While 83% of the patients were affected by behavioural and neuropsychiatric symptoms of dementia, behavioural disinhibition and decline in executive function were most common in FTD patients. Recurrent hallucinations, fluctuation of consciousness, parkinsonism, and rapid eye movement sleep behaviour disorder were most common in DLB. Memory impairment and apathy are not useful discriminative symptoms in diagnosing AD, DLB, and FTD. Apraxia favours AD. Hallucinations, particularly well-formed visual hallucinations, favour DLB. Overall, behavioural and neuropsychiatric symptoms of dementia symptoms are common among the three groups of dementia patients.

Shea YF ，Ha J ，Chu LW 《-》