CSF p-Tau levels in the prediction of Alzheimer's disease (original) (raw)
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Cerebrospinal Fluid Tau and Phosphotau As Biomarkers in Alzheimer's Disease Diagnosis
Basic and Clinical Neuroscience Journal
Dementia is a progressive disorder that leads to memory loss and cognition impairment and affects daily function. Alzheimer disease (AD) is the main cause of dementia that characterized by loss of memory and cognition. AD pathologically is demonstrated by neuronal atrophy, synapse loss and the unusual reposition of amyloid-β protein (Aβ) as senile plaques and hyperphosphorylated tau protein as neurofibrillary tangles (NFT). Tau is a microtubule associated protein mostly expressed in neurons. Site-specific phosphorylation regulates Tau function. In AD, the six adult tau isoforms are unusually phosphorylated that cause to form the paired helical filament. The different conditions of tau phosphorylation eventuate from the function of specific kinases and phosphatases. In recent years some biomarkers such as phospho tau 181, 199 and 231 had been assessed in cerebrospinal fluid (CSF) and blood and had been showed their elevation in AD. This article provides an overview of tau structure, functions, and its involvement in AD and its role as a CSF biomarker.
P CSF Levels of Tau Protein and Beta Amyloid in Diagnosis of Alzheimer ́ S Disease
2004
About two thirds of cases of senile dementia are due to Alzheimer ́s disease (AD). Definite diagnosis of AD is based on the neuropathological changes in the brain characterized by the presence of senile amyloid plaques, neurofibrillary tangles and neuronal cell loss. Sensitive assays showed the presence of tau and beta amyloid in CSF and change in levels of these molecules have been suggested to be a possible markers of AD. Cerebrospinal fluid samples from total of 102 subjects consisting of 24 patients with AD and 78 control patients with other neurological diseases were examined by ELISA of tau protein and beta amyloid (Innogenetics, Belgium). As compared to the control group, the concentrations of tau protein were significantly higher in AD patients (p < 0.0001) in contrast to levels of beta amyloid, where are significantly decreased (p < 0.0001). ROC (Receiver Operating Characteristic) analysis was performed to define cut-off values for maximized sensitivity and specificit...
Arquivos de Neuro-Psiquiatria, 2004
Alzheimer's disease (AD) is pathologically characterized by the accumulation of amyloid plaques and tau-associated neurofibrillary tangles in the cerebral tissue. The search for antemortem biomarkers is intense including analysis of cerebrospinal fluid (CSF) beta-amyloid and tau proteins concentrations seeking for an accurate and early diagnosis. Levels of hyperphosphorylated tau at threonine 181 were measured in the CSF of 34 patients with AD (19 with senile AD - SAD and eight with presenile AD - PSAD) and seven with other dementias (OD). The levels of CSF phosphotau were significantly higher in the AD patients compared to OD (AUC 0.812), with no association with severity of dementia, age of onset, duration of the disease or scores in the Mini-Mental State Examination. There were no differences of phosphotau levels between SAD and PSAD patients. These findings corroborate some previous studies and indicate that CSF phosphotau may help to differentiate AD from other dementias.
Journal of the Medical Association of Thailand = Chotmaihet thangphaet, 2011
The combination of decreased cerebrospinal fluid (CSF) levels of beta-amyloid (1-42) and increased levels of phosphorylated tau (ptau-181) or total tau protein are known to be biomarkers ofAlzheimer's disease (AD). These biomarkers can also be used as predictors of disease progression in persons with mild cognitive impairment. Utilizing biomarkers to differentiate Alzheimer's disease (AD) against non-Alzheimer dementia (non-AD) needs to be explored. To evaluate the clinical use ofCSF biomarker: beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein for distinguishing Alzheimer's disease (AD) from non-Alzheimer dementia (non-AD) in Thai patients. Thirty patients diagnosed of dementia during 2005-2007 at Siriraj hospital were offered CSF analysis for beta-amyloid (1-42), phosphorylated tau (ptau-181) and total tau protein. Diagnosis of dementia was performed by a concensus diagnostic group utilizing a standard criteria for diagnosis of AD and other dement...
Journal of Neurology, Neurosurgery & Psychiatry, 1998
Biochemical markers for Alzheimer&amp;amp;amp;#39;s disease would be of great value, especially to help in diagnosis early in the course of the disease. A pronounced increase in CSF tau protein (CSF-tau) is found in most patients with Alzheimer&amp;amp;amp;#39;s disease. However, the specificity has to be further studied, as an increase in CSF-tau has also been found in other dementias, especially in vascular dementia. As most previous CSF studies have been based on selected inpatients, it was considered of special interest to examine the diagnostic potential of CSF-tau in a community population based sample of consecutive patients with dementia. Such patient material has been examined at the Piteå River Valley Hospital in Northern Sweden since 1986, and includes all those with memory disturbances in the community. The aim was also to study if an increase in CSF-tau is found early in the disease process, and whether CSF-tau changes during the progression of disease. Community population based sample of 75 demented patients (43 with Alzheimer&amp;amp;amp;#39;s disease, 21 with vascular dementia, and 11 with mixed Alzheimer&amp;amp;amp;#39;s disease/vascular dementia), 18 healthy subjects, and 18 neurological controls. A follow up investigation (including analysis of a new CSF sample) was performed in all patients after about one year. Concentrations of total (both normal tau and PHF-tau) tau in CSF, clinical measures (duration and severity of dementia), and apoE polymorphism. CSF-tau was markedly increased in Alzheimer&amp;amp;amp;#39;s disease, 41/43 (95%) patients had values above the cut off level (mean+2 SD) in controls (306 pg/ml). High CSF-tau concentrations were also found in most patients with vascular dementia, preferentially in patients with vascular dementia without progressive leukoaraiosis on CT, whereas patients with vascular dementia with progressive leukoaraiosis had normal CSF-tau. Concentrations of CSF-tau were stable at one year follow up in both patients with Alzheimer&amp;amp;amp;#39;s disease and patients with vascular dementia, and there was no correlation between CSF-tau and either duration or severity of dementia. The findings confirm the high sensitivity of CSF-tau for the diagnosis of Alzheimer&amp;amp;amp;#39;s disease, but high CSF-tau was also found in vascular dementia, resulting in a lower specificity. However, high CSF-tau is preferentially found in patients with vascular dementia without progressive leukoaraiosis, which may constitute a group with concomitant Alzheimer&amp;amp;amp;#39;s disease pathology. High CSF-tau may be present during the whole course of the disease in Alzheimer&amp;amp;amp;#39;s disease. Possibly, therefore, the same high CSF-tau concentrations may be present before the onset of clinical dementia. Follow up studies on such patients will tell whether analysis of CSF-tau is useful as a biochemical marker for early Alzheimer&amp;amp;amp;#39;s disease.
CNS neuroscience & therapeutics, 2018
The diagnosis of either Alzheimer's disease (AD) or vascular dementia (VaD) is still largely based on clinical guidelines and exclusion of other diseases that may lead to dementia. In this study, we assessed whether the use of sensitive and specific biomarkers such as phosphorylated tau proteins could contribute to an earlier and more accurate diagnosis of AD and VaD, as well as to their differentiation. A total of 198 patients, of which 152 had AD, 28 VaD, and 18 were healthy controls (HC), were included in the analyses. We analyzed cerebrospinal fluid (CSF) levels of total tau protein (t-tau), tau protein phosphorylated at threonine 231 (p-tau231), and factor score (FS) determined by combination of p-tau231 and Mini-Mental State Examination (MMSE) in patients with AD and VaD, as well as in HC. We tested the diagnostic accuracy of these biomarkers in the CSF and FS (p-tau231, MMSE) in differentiating AD from VaD and HC. Total tau levels were significantly elevated in subjects w...
Clinical and experimental neurology, 2017
Background: Alzheimer’s disease is one of the common causes of dementia in our country. The growth of the elderly population, together with the rising incidence of dementia requires immediate attention. There is very limited data regarding how CSF Tau protein correlates with this group of people’s cognitive function. Objectives: To evaluate association of CSF Tau protein in different types of dementia patients (AD and non-AD) and to find out the correlation of CSF Tau with severity of dementia and duration of disease. Methods: This cross sectional analytical study was conducted in dementia clinic (OPD) and inpatient department of Neurology, BSMMU from March’2013 to September’2015. 48 both male and female adult subjects were included in this study. Then they were divided into 3 groups: Alzheimer’s disease (AD) group (n=15), non-AD other dementias (OD) group (n=18) and subjects having neither AD and/or OD were included as control (n=15). CSF Tau protein was measured and compared betwe...
CSF-phospho-tau as a promising marker for discriminating Alzheimer disease from Lewy body dementia
Neurobiology of Aging, 2000
Background: Total tau (T-tau) and b-amyloid (1-42) (Ab 1-42 ) levels in cerebrospinal fluid (CSF) can differentiate Alzheimer's disease (AD) from normal aging or depressive pseudo-dementia. Differential diagnosis from dementia with Lewy bodies (DLB) in clinical settings is difficult. Methods: The analytical performance of the INNO-TEST ᮋ PHOSPHO-TAU (181P) assay was validated in terms of selectivity, sensitivity, specificity, precision, robustness, and stability. Clinical utility of the assay alone, or combined with T-tau and Ab 1-42 , for discrimination of AD (ns94) from patients suffering from DLB (ns60) or from age-matched control subjects (CS) (ns60) was assessed in a multicenter study. Results: CSF concentrations of tau phosphorylated at threonine 181 (P-tau 181P ) in AD was significantly higher than in DLB and CS. Discriminant analysis, a classification tree, and logistic regression showed that P-tau 181P was the most statistically significant single variable of the three biomarkers for discrimination between AD and DLB. Conclusions: P-tau 181P quantification is a robust and reliable assay that may be useful in discriminating AD from DLB.
Plasma tau complements CSF tau and P-tau in the diagnosis of Alzheimer's disease
Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Introduction: Plasma tau may be an accessible biomarker for Alzheimer's disease (AD), but the correlation between plasma and cerebrospinal fluid (CSF) tau and the value of combining plasma tau with CSF tau and phospho-tau (P-tau) are still unclear. Methods: Plasma-tau, CSF-tau, and P-tau were measured in 97 subjects, including elderly cognitively normal controls (n 5 68) and patients with AD (n 5 29) recruited at the NYU Center for Brain Health, with comprehensive neuropsychological and magnetic resonance imaging evaluations. Results: Plasma tau was higher in patients with AD than cognitively normal controls (P , .001, area under the receiver operating characteristic curve 5 0.79) similarly to CSF tau and CSF P-tau and was negatively correlated with cognition in AD. Plasma and CSF tau measures were poorly correlated. Adding plasma tau to CSF tau or CSF P-tau significantly increased the areas under the receiver operating characteristic curve from 0.80 and 0.82 to 0.87 and 0.88, respectively. Discussion: Plasma tau is higher in AD independently from CSF-tau. Importantly, adding plasma tau to CSF tau or P-tau improves diagnostic accuracy, suggesting that plasma tau may represent a useful biomarker for AD, especially when added to CSF tau measures.