Phospho-tau/total tau ratio in cerebrospinal fluid discriminates Creutzfeldt-Jakob disease from other dementias

被引:174
作者
Riemenschneider, M
Wagenpfeil, S
Vanderstichele, H
Otto, M
Wiltfang, J
Kretzschmar, H
Vanmechelen, E
Förstl, H
Kurz, A
机构
[1] Tech Univ Munich, Dept Psychiat & Psychotherapy, D-81675 Munich, Germany
[2] Tech Univ Munich, Dept Psychiat, Neruochem & Neurogenet Lab, D-81675 Munich, Germany
[3] Tech Univ Munich, Inst Med Stat & Epidemiol, D-81675 Munich, Germany
[4] Innogenet NV, Ghent, Belgium
[5] Univ Gottingen, Dept Neurol, D-3400 Gottingen, Germany
[6] Univ Gottingen, Dept Psychiat, D-3400 Gottingen, Germany
[7] Univ Munich, Inst Neuropathol, D-8000 Munich, Germany
关键词
tau; phospho-tau; cerebrospinal fluid; Alzheimer; Creutzfeldt-Jakob disease; frontotemporal degeneration;
D O I
10.1038/sj.mp.4001220
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Early clinical symptoms of sporadic Creutzfeldt-Jakob disease (CJD) may overlap with other neurodegenerative diseases like Alzheimer's disease (AD) and frontotemporal degeneration (FTD). On entering an era in which pharmaceutical treatment of CJD occurs, reliable diagnostic markers like immunodetection of 14-3-3 proteins in the cerebrospinal fluid (CSF) are required. However, false negative results in autopsy-proven, sporadic CJD cases, as well as false positive results in several other disorders including AD and FTD showing high CSF tau protein levels, limit the potential of this marker. Due to neuronal lysis the cytosolic fraction of total tau containing phosphorylated and non-phosphorylated isoforms is partially liberated into the CSF. Since hyperphosphorylation of tau may specifically occur in neurodegenerative diseases associated with neurofibrillary changes, we hypothesized that the phospho-tau (P-tau)/total tau ratio in CSF may be a useful marker to discriminate CJD from other neurodegenerative disorders. The P-tau/total tau ratio discriminated patients with CJD from all other neurodegenerative disorders including patients with AD and FTD without any overlap. Although the results have to be confirmed in a larger sample, the preliminary data suggest that simultaneous measurement of total tau and P-tau in CSF may be useful to identify patients with CJD.
引用
收藏
页码:343 / 347
页数:5
相关论文
共 20 条
[1]   CSF detection of the 14-3-3 protein in unselected patients with dementia [J].
Burkhard, PR ;
Sanchez, JC ;
Landis, T ;
Hochstrasser, DF .
NEUROLOGY, 2001, 56 (11) :1528-1533
[2]   Increased tau in the cerebrospinal fluid of patients with frontotemporal dementia and Alzheimer's disease [J].
Green, AJE ;
Harvey, RJ ;
Thompson, EJ ;
Rossor, MN .
NEUROSCIENCE LETTERS, 1999, 259 (02) :133-135
[3]   ELISA-quantitation of phosphorylated tau protein in the Alzheimer's disease brain [J].
Herrmann, M ;
Golombowski, S ;
Kräuchi, K ;
Frey, P ;
Mourton-Gilles, C ;
Hulette, C ;
Rosenberg, C ;
Müller-Spahn, F ;
Hock, C .
EUROPEAN NEUROLOGY, 1999, 42 (04) :205-210
[4]   Transient increase in total tau but not phospho-tau in human cerebrospinal fluid after acute stroke [J].
Hesse, C ;
Rosengren, L ;
Andreasen, N ;
Davidsson, P ;
Vanderstichele, H ;
Vanmechelen, E ;
Blennow, K .
NEUROSCIENCE LETTERS, 2001, 297 (03) :187-190
[5]   The 14-3-3 brain protein in cerebrospinal fluid as a marker for transmissible spongiform encephalopathies [J].
Hsich, G ;
Kinney, K ;
Gibbs, CJ ;
Lee, KH ;
Harrington, MG .
NEW ENGLAND JOURNAL OF MEDICINE, 1996, 335 (13) :924-930
[6]   Improved discrimination of AD patients using β-amyloid(1-42) and tau levels in CSF [J].
Hulstaert, F ;
Blennow, K ;
Ivanoiu, A ;
Schoonderwaldt, HC ;
Riemenschneider, M ;
De Deyn, PP ;
Bancher, C ;
Cras, P ;
Wiltfang, J ;
Mehta, PD ;
Iqbal, K ;
Pottel, H ;
Vanmechelen, E ;
Vanderstichele, H .
NEUROLOGY, 1999, 52 (08) :1555-1562
[7]   Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17 [J].
Hutton, M ;
Lendon, CL ;
Rizzu, P ;
Baker, M ;
Froelich, S ;
Houlden, H ;
Pickering-Brown, S ;
Chakraverty, S ;
Isaacs, A ;
Grover, A ;
Hackett, J ;
Adamson, J ;
Lincoln, S ;
Dickson, D ;
Davies, P ;
Petersen, RC ;
Stevens, M ;
de Graaff, E ;
Wauters, E ;
van Baren, J ;
Hillebrand, M ;
Joosse, M ;
Kwon, JM ;
Nowotny, P ;
Che, LK ;
Norton, J ;
Morris, JC ;
Reed, LA ;
Trojanowski, J ;
Basun, H ;
Lannfelt, L ;
Neystat, M ;
Fahn, S ;
Dark, F ;
Tannenberg, T ;
Dodd, PR ;
Hayward, N ;
Kwok, JBJ ;
Schofield, PR ;
Andreadis, A ;
Snowden, J ;
Craufurd, D ;
Neary, D ;
Owen, F ;
Oostra, BA ;
Hardy, J ;
Goate, A ;
van Swieten, J ;
Mann, D ;
Lynch, T .
NATURE, 1998, 393 (6686) :702-705
[8]   Mechanism of Alzheimer neurofibrillary degeneration and the formation of tangles [J].
Iqbal, K ;
GrundkeIqbal, I .
MOLECULAR PSYCHIATRY, 1997, 2 (03) :178-180
[9]   Phosphorylated tau in human cerebrospinal fluid is a diagnostic marker for Alzheimer's disease [J].
Ishiguro, K ;
Ohno, H ;
Arai, H ;
Yamaguchi, H ;
Urakami, K ;
Park, JM ;
Sato, K ;
Kohno, H ;
Imahori, K .
NEUROSCIENCE LETTERS, 1999, 270 (02) :91-94
[10]   Detection of tau phosphorylated at threonine 231 in cerebrospinal fluid of Alzheimer's disease patients [J].
Kohnken, R ;
Buerger, K ;
Zinkowski, R ;
Miller, C ;
Kerkman, D ;
DeBernardis, J ;
Shen, JF ;
Möller, HJ ;
Davies, P ;
Hampel, H .
NEUROSCIENCE LETTERS, 2000, 287 (03) :187-190