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Katharina Buerger - One of the best experts on this subject based on the ideXlab platform.
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csf phosphorylated Tau Protein correlates with neocortical neurofibrillary pathology in alzheimer s disease
Brain, 2006Co-Authors: Katharina Buerger, Stefan J Teipel, Raymond Zinkowski, Cheryl Mcculloch, Michael Ewers, Tuula Pirttila, Irina Alafuzoff, John Debernardis, Daniel J Kerkman, Hilkka SoininenAbstract:Hyperphosphorylated Tau Protein (P-Tau) in CSF is a core biomarker candidate of Alzheimer's disease. Hyperphosphorylation of Tau is thought to lead to neurofibrillary changes, a neuropathological hallmark of this type of dementia. Currently, the question is unresolved whether CSF levels of P-Tau reflect neurofibrillary changes within the brain of a patient with the illness. Twenty-six patients were included with intra-vitam CSF as well as post-mortem neuropathological data. In the CSF, P-Tau phosphorylated at threonine 231 (P-Tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed in frontal, temporal, parietal and hippocampal cortical areas. In the same cortical regions, load of hyperphosphorylated Tau Protein (HP-Tau load) was determined. Concentrations of P-Tau231P were measured in frontal cortex homogenates. We found significant correlations between CSF P-Tau231P concentrations and scores of NFTs and HP-Tau load in all neocortical regions studied. The score of NPs was correlated with CSF P-Tau231P only within the frontal cortex. There was a correlation between P-Tau231P in CSF and brain homogenates. These findings indicate that CSF P-Tau231P may serve as an in vivo surrogate biomarker of neurofibrillary pathology in Alzheimer's disease.
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dissociation between csf total Tau and Tau Protein phosphorylated at threonine 231 in creutzfeldt jakob disease
Neurobiology of Aging, 2006Co-Authors: Katharina Buerger, Markus Otto, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, John Debernardis, Daniel J Kerkman, Johannes Schroder, Peter Schonknecht, Lukas CepekAbstract:To study the potential diagnostic value of abnormally phosphorylated Tau Protein in Creutzfeldt–Jakob disease (CJD) compared to Alzheimer’s disease (AD), we determined levels of Tau phosphorylated at threonine 231 (p-Tau231) and of total Tau (t-Tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-Tau levels but relatively low p-Tau231 concentrations compared to the AD group. t-Tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-Tau231 and the p-Tau231/t-Tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-Tau and p-Tau 231 in CJD when compared to AD.
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differentiation of geriatric major depression from alzheimer s disease with csf Tau Protein phosphorylated at threonine 231
American Journal of Psychiatry, 2003Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Cheryl Mcculloch, John Debernardis, Daniel J Kerkman, Frank Padberg, Frank Faltraco, Alexander GoernitzAbstract:OBJECTIVE: Differentiation of geriatric major depression from Alzheimer’s disease is hampered by overlapping symptoms. Increased CSF concentrations of Tau Protein phosphorylated at threonine 231 (p-Tau231) have been suggested as a biomarker for Alzheimer’s disease. The authors asked whether p-Tau231 levels improve the differential diagnosis between geriatric major depression and Alzheimer’s disease. METHOD: Included were 34 depression subjects, 64 with probable Alzheimer’s disease, 17 with possible Alzheimer’s disease, and 21 healthy comparison subjects. P-Tau231 concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: P-Tau231 levels were significantly higher in Alzheimer’s disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer’s disease from major depression, p-Tau231 correctly allocated 87% of subjects. When possible mild Alzheimer’s disease was compared to major depression, p-Tau231 correctly allocated 78% ...
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csf Tau Protein phosphorylated at threonine 231 correlates with cognitive decline in mci subjects
Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, Rolf R Engel, K Hofmannkiefer, Cheryl Mcculloch, Ursula Ptok, Reinhard HeunAbstract:In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of Tau Protein phosphorylated at threonine 231 (p-Tau231) in CSF correlate with progression of cognitive decline. High CSF p-Tau231 levels at baseline, but not total Tau Protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-e4 carrier status were predictive as well. Our data indicate that an increased p-Tau231 level is a potential risk factor for cognitive decline in patients with MCI.
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differential diagnosis of alzheimer disease with cerebrospinal fluid levels of Tau Protein phosphorylated at threonine 231
JAMA Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, K Hofmannkiefer, Tero Tapiola, Niels Andreasen, John DebernardisAbstract:Background: Phosphorylation of Tau Protein at threonine 231 (using full-length Tau, 441 amino acids, for the numbering scheme) (p-Tau231) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-Tau231 distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-Tau231 levels are a better diagnostic marker than levels of total Tau Protein (t-Tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic–based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Results: Mean CSF levels of p-Tau231 were significantly elevated in the AD group compared with all other groups. Levels of p-Tau231 did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-Tau231 levels improved diagnostic accuracy compared with t-Tau levels when patients with AD were compared with healthy controls (P=.03) and demented subjects (P.001), particularly those with FTD (P.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-Tau231 compared with tTau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-Tau231 may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
Markus Otto - One of the best experts on this subject based on the ideXlab platform.
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total Tau Protein phosphorylated Tau 181p Protein β amyloid1 42 and β amyloid1 40 in cerebrospinal fluid of patients with dementia with lewy bodies
Clinical Chemistry and Laboratory Medicine, 2006Co-Authors: Brit Mollenhauer, Jens Wiltfang, Barbara Ciesielczyk, Mirko Bibl, Petra Steinacker, Karin Neubert, Claudia Trenkwalder, Markus OttoAbstract:The intra vitam diagnosis of different dementias is still based on clinical grounds. So far, no technical investigations have been available to support these diagnoses. For Tau Protein and beta-amyloid(1-42) in cerebrospinal fluid (CSF), promising results for the diagnosis of Alzheimer's disease (AD) have been reported; however, their differential diagnostic spectrum is limited, as was recently shown for dementia with Lewy bodies (DLB) and for AD. Therefore, further marker Proteins have to be established to ameliorate, support, and differentiate these clinical diagnoses. We evaluated beta-amyloid(1-40) and phosphorylated Tau Protein (181p), in addition to total Tau Protein and beta-amyloid(1-42), in 20 patients with DLB, 34 AD patients, and 20 non-demented neurological controls (NDCs). All markers could differentiate between the dementia groups (AD, DLB) and the controls. AD and DLB could be differentiated only by levels of total Tau Protein and by the ratio total Tau Protein/phosphorylated Tau Protein. However, values still overlapped markedly. In some cases, Tau Protein levels in CSF may contribute to the clinical distinction between DLB and AD, but the value of the markers is still limited, especially because of mixed pathology. We conclude that more specific markers have to be established to differentiate between these diseases.
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dissociation between csf total Tau and Tau Protein phosphorylated at threonine 231 in creutzfeldt jakob disease
Neurobiology of Aging, 2006Co-Authors: Katharina Buerger, Markus Otto, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, John Debernardis, Daniel J Kerkman, Johannes Schroder, Peter Schonknecht, Lukas CepekAbstract:To study the potential diagnostic value of abnormally phosphorylated Tau Protein in Creutzfeldt–Jakob disease (CJD) compared to Alzheimer’s disease (AD), we determined levels of Tau phosphorylated at threonine 231 (p-Tau231) and of total Tau (t-Tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-Tau levels but relatively low p-Tau231 concentrations compared to the AD group. t-Tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-Tau231 and the p-Tau231/t-Tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-Tau and p-Tau 231 in CJD when compared to AD.
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aβ peptide1 42 Tau Protein and s 100b Protein level in cerebrospinal fluid of three patients with primary progressive aphasia
Neuroscience Letters, 2002Co-Authors: Lienhard Maeck, Markus Otto, Jens Wiltfang, J Meller, Gerthild Stiens, Gabriela StoppeAbstract:Abstract Primary progressive aphasia (PPA) is a clinical syndrome characterized by a slowly progressive aphasia in the absence of accompanying signs of generalized dementia. While non-fluent PPA tends to progress frontally and is usually linked to frontotemporal degeneration, fluent PPA might be associated with both, frontotemporal degeneration or Alzheimer's disease. Although recent reports suggest that PPA belongs neuropathologically to the group of Tauopathias, cerebrospinal fluid analysis has not been established as a means of diagnosis in PPA so far. In this paper we investigated Aβ peptide1–42 (Aβ1–42), Tau Protein and S-100B Protein level in the cerebrospinal fluid of three patients with PPA. In all patients Tau Protein and S-100B level were slightly elevated, however, Aβ1–42 was found to be in normal range. Thus, our first results point to PPA being neurochemically linked to frontotemporal degeneration.
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Tau Protein and 14 3 3 Protein in the differential diagnosis of creutzfeldt jakob disease
Neurology, 2002Co-Authors: Markus Otto, Jens Wiltfang, Lukas Cepek, Manuela Neumann, Brit Mollenhauer, P Steinacker, Barbara Ciesielczyk, Walter J Schulzschaeffer, H A Kretzschmar, S PoserAbstract:Background: Diagnosis of Creutzfeldt–Jakob disease (CJD) is made according to the typical clinical picture and can be supported by a positive 14-3-3 CSF immunoblot. Promising results for the diagnostic sensitivity and specificity of Tau-Protein measurement in CSF already have been described in a smaller group of patients. Both tests in a larger group of patients with the differential diagnosis of CJD were evaluated. Methods: CSF of 297 patients under the differential diagnosis of CJD (109 definite, 55 probable, 39 possible; 85 others, 1 iatrogenic, 8 genetic), 23 nondemented control subjects, and 15 non-CJD patients with positive 14-3-3 immunoblots were analyzed. The 14-3-3 immunoblot bands were semiquantitatively rated as strong, medium, and weak. Tau-Protein was analyzed using a commercially available ELISA. In addition, patients were neuropathologically classified according to prion Protein type and polymorphism at codon 129. Results: A diagnostic sensitivity of 94%, a diagnostic specificity of 90%, and a positive predictive value of 92% were achieved for Tau-Protein at a cut-off of 1,300 pg/mL. These results are comparable with those of the 14-3-3 immunoblot. For patients with type II prion Protein and methionine/valine or valine/valine polymorphism at codon 129, Tau-Protein has a higher diagnostic sensitivity than 14-3-3 Protein. Tau-Protein levels were significantly higher in patients with higher-rated 14-3-3 immunoblot bands. Conclusion: The differential diagnostic significance of the 14-3-3 immunoblot is similar to that of the Tau-Protein ELISA. The advantage of the Tau-Protein ELISA is that it is easy to use in routine laboratories. Patients with a negative 14-3-3 immunoblot already have measurable Tau-Protein levels. This increases information on 14-3-3—negative patients with CJD and especially on patients with other diseases.
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elevated levels of Tau Protein in cerebrospinal fluid of patients with creutzfeldt jakob disease
Neuroscience Letters, 1997Co-Authors: Markus Otto, Jens Wiltfang, H A Kretzschmar, Hayrettin Tumani, Inga Zerr, Maria Lantsch, Johannes Kornhuber, T Weber, S PoserAbstract:Creutzfeldt-Jakob disease (CJD) is a rare, fatal, neurodegenerative disease caused by a transmissible agent designated as Proteinaceous infectious agent (prion). Searching for biochemical markers of CJD, we analysed cerebrospinal fluid (CSF) samples of 53 patients for Tau-Protein using an enzyme linked immunoassay (ELISA). In a group of 21 patients with definite CJD seen in the German case control study for CJD, Tau-Protein concentrations in CSF were significantly higher than in two control-groups of patients with other diseases (median 13,153 pg/ml, range 1,533-27,648 pg/ml; P = 0.0001). One group comprised 19 patients who were seen in the same study and were diagnosed as having other dementing diseases (Tau concentration: median 558 pg/ml, range 233-1,769 pg/ml). The second control group comprised 13 patients from our hospital with no dementing disease (Tau concentration: median 296 pg/ml, range 109-640 pg/ml). We conclude that determination of Tau Protein levels in CSF is a useful marker for laboratory diagnosis of CJD.
Hiroyuki Arai - One of the best experts on this subject based on the ideXlab platform.
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use of a benzimidazole derivative bf 188 in fluorescence multispectral imaging for selective visualization of Tau Protein fibrils in the alzheimer s disease brain
Molecular Imaging and Biology, 2014Co-Authors: Ryuichi Harada, Nobuyuki Okamura, Shozo Furumoto, Takeo Yoshikawa, Hiroyuki Arai, Kazuhiko Yanai, Yukitsuka KudoAbstract:Purpose Selective visualization of amyloid-β and Tau Protein deposits will help to understand the pathophysiology of Alzheimer’s disease (AD). Here, we introduce a novel fluorescent probe that can distinguish between these two deposits by multispectral fluorescence imaging technique.
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differentiation of geriatric major depression from alzheimer s disease with csf Tau Protein phosphorylated at threonine 231
American Journal of Psychiatry, 2003Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Cheryl Mcculloch, John Debernardis, Daniel J Kerkman, Frank Padberg, Frank Faltraco, Alexander GoernitzAbstract:OBJECTIVE: Differentiation of geriatric major depression from Alzheimer’s disease is hampered by overlapping symptoms. Increased CSF concentrations of Tau Protein phosphorylated at threonine 231 (p-Tau231) have been suggested as a biomarker for Alzheimer’s disease. The authors asked whether p-Tau231 levels improve the differential diagnosis between geriatric major depression and Alzheimer’s disease. METHOD: Included were 34 depression subjects, 64 with probable Alzheimer’s disease, 17 with possible Alzheimer’s disease, and 21 healthy comparison subjects. P-Tau231 concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: P-Tau231 levels were significantly higher in Alzheimer’s disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer’s disease from major depression, p-Tau231 correctly allocated 87% of subjects. When possible mild Alzheimer’s disease was compared to major depression, p-Tau231 correctly allocated 78% ...
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csf Tau Protein phosphorylated at threonine 231 correlates with cognitive decline in mci subjects
Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, Rolf R Engel, K Hofmannkiefer, Cheryl Mcculloch, Ursula Ptok, Reinhard HeunAbstract:In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of Tau Protein phosphorylated at threonine 231 (p-Tau231) in CSF correlate with progression of cognitive decline. High CSF p-Tau231 levels at baseline, but not total Tau Protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-e4 carrier status were predictive as well. Our data indicate that an increased p-Tau231 level is a potential risk factor for cognitive decline in patients with MCI.
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differential diagnosis of alzheimer disease with cerebrospinal fluid levels of Tau Protein phosphorylated at threonine 231
JAMA Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, K Hofmannkiefer, Tero Tapiola, Niels Andreasen, John DebernardisAbstract:Background: Phosphorylation of Tau Protein at threonine 231 (using full-length Tau, 441 amino acids, for the numbering scheme) (p-Tau231) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-Tau231 distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-Tau231 levels are a better diagnostic marker than levels of total Tau Protein (t-Tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic–based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Results: Mean CSF levels of p-Tau231 were significantly elevated in the AD group compared with all other groups. Levels of p-Tau231 did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-Tau231 levels improved diagnostic accuracy compared with t-Tau levels when patients with AD were compared with healthy controls (P=.03) and demented subjects (P.001), particularly those with FTD (P.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-Tau231 compared with tTau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-Tau231 may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
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diagnostic significance of Tau Protein in cerebrospinal fluid from patients with corticobasal degeneration or progressive supranuclear palsy
Journal of the Neurological Sciences, 2001Co-Authors: Katsuya Urakami, Hiroyuki Arai, Kenji Wada, Hiroshi Sasaki, Mitsuyasu Kanai, Mikio Shoji, Hideki Ishizu, Kenichi Kashihara, Mitsutoshi Yamamoto, K TsuchiyaikemotoAbstract:Abstract Distinguishing corticobasal degeneration (CBD) from progressive supranuclear palsy (PSP) is clinically and pathologically difficult, and a useful biological marker to discriminative these two diseases has been a subject of clinical interest. In the present study, we assessed Tau Protein levels in cerebrospinal fluids by sandwich ELISA to distinguish CBD from PSP. The subjects consisted of 27 cases of CBD, 30 cases of PSP, and 36 healthy controls (CTL). The Tau values in CBD were significantly higher than those in PSP (P
John Debernardis - One of the best experts on this subject based on the ideXlab platform.
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csf phosphorylated Tau Protein correlates with neocortical neurofibrillary pathology in alzheimer s disease
Brain, 2006Co-Authors: Katharina Buerger, Stefan J Teipel, Raymond Zinkowski, Cheryl Mcculloch, Michael Ewers, Tuula Pirttila, Irina Alafuzoff, John Debernardis, Daniel J Kerkman, Hilkka SoininenAbstract:Hyperphosphorylated Tau Protein (P-Tau) in CSF is a core biomarker candidate of Alzheimer's disease. Hyperphosphorylation of Tau is thought to lead to neurofibrillary changes, a neuropathological hallmark of this type of dementia. Currently, the question is unresolved whether CSF levels of P-Tau reflect neurofibrillary changes within the brain of a patient with the illness. Twenty-six patients were included with intra-vitam CSF as well as post-mortem neuropathological data. In the CSF, P-Tau phosphorylated at threonine 231 (P-Tau231P) was analysed. Post-mortem, scores of neurofibrillary tangles (NFT) and neuritic plaques (NP) were assessed in frontal, temporal, parietal and hippocampal cortical areas. In the same cortical regions, load of hyperphosphorylated Tau Protein (HP-Tau load) was determined. Concentrations of P-Tau231P were measured in frontal cortex homogenates. We found significant correlations between CSF P-Tau231P concentrations and scores of NFTs and HP-Tau load in all neocortical regions studied. The score of NPs was correlated with CSF P-Tau231P only within the frontal cortex. There was a correlation between P-Tau231P in CSF and brain homogenates. These findings indicate that CSF P-Tau231P may serve as an in vivo surrogate biomarker of neurofibrillary pathology in Alzheimer's disease.
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dissociation between csf total Tau and Tau Protein phosphorylated at threonine 231 in creutzfeldt jakob disease
Neurobiology of Aging, 2006Co-Authors: Katharina Buerger, Markus Otto, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, John Debernardis, Daniel J Kerkman, Johannes Schroder, Peter Schonknecht, Lukas CepekAbstract:To study the potential diagnostic value of abnormally phosphorylated Tau Protein in Creutzfeldt–Jakob disease (CJD) compared to Alzheimer’s disease (AD), we determined levels of Tau phosphorylated at threonine 231 (p-Tau231) and of total Tau (t-Tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-Tau levels but relatively low p-Tau231 concentrations compared to the AD group. t-Tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-Tau231 and the p-Tau231/t-Tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-Tau and p-Tau 231 in CJD when compared to AD.
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differentiation of geriatric major depression from alzheimer s disease with csf Tau Protein phosphorylated at threonine 231
American Journal of Psychiatry, 2003Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Cheryl Mcculloch, John Debernardis, Daniel J Kerkman, Frank Padberg, Frank Faltraco, Alexander GoernitzAbstract:OBJECTIVE: Differentiation of geriatric major depression from Alzheimer’s disease is hampered by overlapping symptoms. Increased CSF concentrations of Tau Protein phosphorylated at threonine 231 (p-Tau231) have been suggested as a biomarker for Alzheimer’s disease. The authors asked whether p-Tau231 levels improve the differential diagnosis between geriatric major depression and Alzheimer’s disease. METHOD: Included were 34 depression subjects, 64 with probable Alzheimer’s disease, 17 with possible Alzheimer’s disease, and 21 healthy comparison subjects. P-Tau231 concentrations were measured with an enzyme-linked immunosorbent assay. RESULTS: P-Tau231 levels were significantly higher in Alzheimer’s disease than in geriatric major depression patients and healthy comparison subjects. For differentiation of probable Alzheimer’s disease from major depression, p-Tau231 correctly allocated 87% of subjects. When possible mild Alzheimer’s disease was compared to major depression, p-Tau231 correctly allocated 78% ...
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differential diagnosis of alzheimer disease with cerebrospinal fluid levels of Tau Protein phosphorylated at threonine 231
JAMA Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, K Hofmannkiefer, Tero Tapiola, Niels Andreasen, John DebernardisAbstract:Background: Phosphorylation of Tau Protein at threonine 231 (using full-length Tau, 441 amino acids, for the numbering scheme) (p-Tau231) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-Tau231 distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-Tau231 levels are a better diagnostic marker than levels of total Tau Protein (t-Tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic–based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Results: Mean CSF levels of p-Tau231 were significantly elevated in the AD group compared with all other groups. Levels of p-Tau231 did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-Tau231 levels improved diagnostic accuracy compared with t-Tau levels when patients with AD were compared with healthy controls (P=.03) and demented subjects (P.001), particularly those with FTD (P.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-Tau231 compared with tTau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-Tau231 may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
Kaj Blennow - One of the best experts on this subject based on the ideXlab platform.
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dissociation between csf total Tau and Tau Protein phosphorylated at threonine 231 in creutzfeldt jakob disease
Neurobiology of Aging, 2006Co-Authors: Katharina Buerger, Markus Otto, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, John Debernardis, Daniel J Kerkman, Johannes Schroder, Peter Schonknecht, Lukas CepekAbstract:To study the potential diagnostic value of abnormally phosphorylated Tau Protein in Creutzfeldt–Jakob disease (CJD) compared to Alzheimer’s disease (AD), we determined levels of Tau phosphorylated at threonine 231 (p-Tau231) and of total Tau (t-Tau) in cerebrospinal fluid (CSF) of CJD patients, AD patients, and healthy controls (HC). CJD patients showed excessively high t-Tau levels but relatively low p-Tau231 concentrations compared to the AD group. t-Tau alone yielded the best diagnostic accuracy to differentiate between CJD and AD patients, when compared to p-Tau231 and the p-Tau231/t-Tau ratio (97, 78, and 95% correctly allocated cases, respectively). Our findings indicate a dissociation in the direction of change in CSF levels of t-Tau and p-Tau 231 in CJD when compared to AD.
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csf Tau Protein phosphorylated at threonine 231 correlates with cognitive decline in mci subjects
Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, Rolf R Engel, K Hofmannkiefer, Cheryl Mcculloch, Ursula Ptok, Reinhard HeunAbstract:In this longitudinal study of 77 patients with mild cognitive impairment (MCI), the authors analyzed whether levels of Tau Protein phosphorylated at threonine 231 (p-Tau231) in CSF correlate with progression of cognitive decline. High CSF p-Tau231 levels at baseline, but not total Tau Protein levels, correlated with cognitive decline and conversion from MCI to AD. Independently, old age and APOE-e4 carrier status were predictive as well. Our data indicate that an increased p-Tau231 level is a potential risk factor for cognitive decline in patients with MCI.
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differential diagnosis of alzheimer disease with cerebrospinal fluid levels of Tau Protein phosphorylated at threonine 231
JAMA Neurology, 2002Co-Authors: Katharina Buerger, Hiroyuki Arai, Stefan J Teipel, Raymond Zinkowski, Kaj Blennow, K Hofmannkiefer, Tero Tapiola, Niels Andreasen, John DebernardisAbstract:Background: Phosphorylation of Tau Protein at threonine 231 (using full-length Tau, 441 amino acids, for the numbering scheme) (p-Tau231) occurs specifically in postmortem brain tissue of patients with Alzheimer disease (AD) and can be sensitively detected in cerebrospinal fluid (CSF). Objectives: To determine to what extent CSF levels of p-Tau231 distinguish patients with AD from control subjects and from patients with other dementias, and to investigate whether p-Tau231 levels are a better diagnostic marker than levels of total Tau Protein (t-Tau) in CSF. Design and Setting: Cross-sectional, multicenter, memory clinic–based studies. Participants: One hundred ninety-two patients with a clinical diagnosis of AD, frontotemporal dementia (FTD), vascular dementia, Lewy body dementia, or other neurological disorder and healthy controls. Results: Mean CSF levels of p-Tau231 were significantly elevated in the AD group compared with all other groups. Levels of p-Tau231 did not correlate with dementia severity in AD, and discriminated with a sensitivity of 90.2% and a specificity of 80.0% between AD and all non-AD disorders. Moreover, p-Tau231 levels improved diagnostic accuracy compared with t-Tau levels when patients with AD were compared with healthy controls (P=.03) and demented subjects (P.001), particularly those with FTD (P.001), but not those with vascular and Lewy body dementias. Sensitivity levels between AD and FTD were raised by p-Tau231 compared with tTau levels from 57.7% to 90.2% at a specificity level of 92.3% for both markers. Conclusion: Increased levels of CSF p-Tau231 may be a useful, clinically applicable biological marker for the differential diagnosis of AD, particularly for distinguishing AD from FTD.
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csf total Tau aβ42 and phosphorylated Tau Protein as biomarkers for alzheimer s disease
Molecular Neurobiology, 2001Co-Authors: Kaj Blennow, Eugeen Vanmechelen, Harald HampelAbstract:With the arrival of effective symptomatic treatments and the promise of drugs that may delay progression, we now need to identify Alzheimer’s disease (AD) at an early stage of the disease. To diagnose AD earlier and more accurately, attention has been directed toward peripheral biochemical markers. This article reviews promising potential cerebrospinal fluid (CSF) biomarkers for AD focussing on their role in clinical diagnosis. In particular, two biochemical markers, CSF total Tau (t-Tau) Protein and the 42 amino acid form of β-amyloid (Aβ42), perform satisfactorily enough to achieve a role in the clinical diagnostic settings of patients with dementia together with the cumulative information from basic clinical work-up, genetic screening, and brain imaging. These CSF markers are particularly useful to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias. In order to discriminate AD from other primary dementia disorders, however, more accurate and specific markers are needed. Preliminary evidence strongly suggests that quantification of Tau phosphorylated at specific sites in CSF improves early detection, differential diagnosis, and tracking of disease progression in AD.
