| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
From Innogenetics NV (Drs. Hulstaert, Pottel, Vanmechelen, and Vanderstichele), Ghent; Laboratory of Neurochemistry (Dr. Ivanoiu), Cliniques Universitaires Saint-Luc, Brussels; Department of Neurology (Dr. De Deyn), AZ Middelheim and University of Antwerp; Department of Neurology (Dr. Cras), University Hospital Antwerp, Belgium; Department of Clinical Neuroscience (Dr. Blennow), Unit of Neurochemistry, University of Göteborg, Sweden; Department of Neurology, University Hospital (Dr. Schoonderwaldt), Nijmegen, the Netherlands; Department of Psychiatry (Dr. Riemenschneider), Technische Universität, Munich; Department of Psychiatry (Dr. Wiltfang), Georg-August University, Göttingen, Germany; Department of Neurology and Ludwig Boltzmann Institute of Clinical Neurobiology (Dr. Bancher), Lainz Hospital, Vienna, Austria; Chemical Neuropathology Laboratory (Dr. Mehta), Institute for Basic Research in Developmental Disabilities; Institute for Basic Research in Developmental Disabilities (Dr. Iqbal), New York, NY.
Address correspondence and reprint requests to Dr. Frank Hulstaert, Innogenetics NV, Industriepark Zwijnaarde 7, Box 4, B-9052 Ghent, Belgium.
OBJECTIVE: To evaluate CSF levels of ß-amyloid(1-42) (Aß42) alone and in combination with CSF tau for distinguishing AD from other conditions.
METHODS: At 10 centers in Europe and the United States, 150 CSF samples from AD patients were analyzed and compared with 100 CSF samples from healthy volunteers or patients with disorders not associated with pathologic conditions of the brain (CON), 84 patients with other neurologic disorders (ND), and 79 patients with non-Alzheimer types of dementia (NAD). Sandwich ELISA techniques were used on site for measuring Aß42 and tau.
RESULTS: Median levels of Aß42 in CSF were significantly lower in AD (487 pg/mL) than in CON (849 pg/mL; p = 0.001), ND (643 pg/mL; p = 0.001), and NAD (603 pg/mL; p = 0.001). Discrimination of AD from CON and ND was significantly improved by the combined assessment of Aß42 and tau. At 85% sensitivity, specificity of the combined test was 86% (95%
CI: 81% to 91%) compared with 55% (95%
CI: 47% to 62%) for Aß42 alone and 65% (95%
CI: 58% to 72%) for tau. The combined test at 85% sensitivity was 58% (95%
CI: 47% to 69%) specific for NAD. The APOE e4 gene load was negatively correlated with Aß42 levels not only in AD but also in NAD.
CONCLUSIONS: The combined measure of CSF Aß42 and tau meets the requirements for clinical use in discriminating AD from normal aging and specific neurologic disorders.
This article has been cited by other articles:
|
|
 |
|
  M. I. Kester, A. E. van der Vlies, M. A. Blankenstein, Y.A.L. Pijnenburg, E. J. van Elk, P. Scheltens, and W. M. van der Flier CSF biomarkers predict rate of cognitive decline in Alzheimer disease Neurology, October 27, 2009; 73(17): 1353 - 1358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A Tarnaris, A K Toma, M D Chapman, A Petzold, N D Kitchen, G Keir, and L D Watkins The longitudinal profile of CSF markers during external lumbar drainage J. Neurol. Neurosurg. Psychiatry, October 1, 2009; 80(10): 1130 - 1133. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N A Verwey, W M van der Flier, K Blennow, C Clark, S Sokolow, P P De Deyn, D Galasko, H Hampel, T Hartmann, E Kapaki, et al. A worldwide multicentre comparison of assays for cerebrospinal fluid biomarkers in Alzheimer's disease Ann Clin Biochem, May 1, 2009; 46(3): 235 - 240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Ringman, S. G. Younkin, D. Pratico, W. Seltzer, G. M. Cole, D. H. Geschwind, Y. Rodriguez-Agudelo, B. Schaffer, J. Fein, S. Sokolow, et al. Biochemical markers in persons with preclinical familial Alzheimer disease Neurology, July 8, 2008; 71(2): 85 - 92. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Klyubin, V. Betts, A. T. Welzel, K. Blennow, H. Zetterberg, A. Wallin, C. A. Lemere, W. K. Cullen, Y. Peng, T. Wisniewski, et al. Amyloid {beta} Protein Dimer-Containing Human CSF Disrupts Synaptic Plasticity: Prevention by Systemic Passive Immunization J. Neurosci., April 16, 2008; 28(16): 4231 - 4237. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Ringman, P. N. Rao, P. H. Lu, and S. Cederbaum Mosaicism for Trisomy 21 in a Patient With Young-Onset Dementia: A Case Report and Brief Literature Review Arch Neurol, March 1, 2008; 65(3): 412 - 415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Nielsen, L. Minthon, E. Londos, K. Blennow, E. Miranda, J. Perez, D. C. Crowther, D. A. Lomas, and S. M. Janciauskiene Plasma and CSF serpins in Alzheimer disease and dementia with Lewy bodies Neurology, October 16, 2007; 69(16): 1569 - 1579. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Brouwers, K. Nuytemans, J. van der Zee, I. Gijselinck, S. Engelborghs, J. Theuns, S. Kumar-Singh, B. A. Pickut, P. Pals, B. Dermaut, et al. Alzheimer and Parkinson Diagnoses in Progranulin Null Mutation Carriers in an Extended Founder Family Arch Neurol, October 1, 2007; 64(10): 1436 - 1446. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Engelborghs, K. Sleegers, P. Cras, N. Brouwers, S. Serneels, E. De Leenheir, J.-J. Martin, E. Vanmechelen, C. Van Broeckhoven, and P. P. De Deyn No association of CSF biomarkers with APOE{varepsilon}4, plaque and tangle burden in definite Alzheimer's disease Brain, September 1, 2007; 130(9): 2320 - 2326. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Li, I. Sokal, J. F. Quinn, J. B. Leverenz, M. Brodey, G. D. Schellenberg, J. A. Kaye, M. A. Raskind, J. Zhang, E. R. Peskind, et al. CSF tau/A{beta}42 ratio for increased risk of mild cognitive impairment: A follow-up study Neurology, August 14, 2007; 69(7): 631 - 639. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R Gustafson, I. Skoog, L. Rosengren, H. Zetterberg, and K. Blennow Cerebrospinal fluid {beta}-amyloid 1-42 concentration may predict cognitive decline in older women J. Neurol. Neurosurg. Psychiatry, May 1, 2007; 78(5): 461 - 464. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. S.M. Reijn, M. O. Rikkert, W. J.A. van Geel, D. de Jong, and M. M. Verbeek Diagnostic Accuracy of ELISA and xMAP Technology for Analysis of Amyloid {beta}42 and Tau Proteins Clin. Chem., May 1, 2007; 53(5): 859 - 865. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ost, K. Nylen, L. Csajbok, A. O. Ohrfelt, M. Tullberg, C. Wikkelso, P. Nellgard, L. Rosengren, K. Blennow, and B. Nellgard Initial CSF total tau correlates with 1-year outcome in patients with traumatic brain injury. Neurology, November 14, 2006; 67(9): 1600 - 1604. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Brouwers, K. Sleegers, S. Engelborghs, V. Bogaerts, S. Serneels, K. Kamali, E. Corsmit, E. D. Leenheir, J.-J. Martin, P. P. De Deyn, et al. Genetic risk and transcriptional variability of amyloid precursor protein in Alzheimer's disease Brain, November 1, 2006; 129(11): 2984 - 2991. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Squitti, G. Barbati, L. Rossi, M. Ventriglia, G. Dal Forno, S. Cesaretti, F. Moffa, I. Caridi, E. Cassetta, P. Pasqualetti, et al. Excess of nonceruloplasmin serum copper in AD correlates with MMSE, CSF {beta}-amyloid, and h-tau. Neurology, July 11, 2006; 67(1): 76 - 82. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Galimberti, N. Schoonenboom, P. Scheltens, C. Fenoglio, F. Bouwman, E. Venturelli, I. Guidi, M. A. Blankenstein, N. Bresolin, and E. Scarpini Intrathecal chemokine synthesis in mild cognitive impairment and Alzheimer disease. Arch Neurol, April 1, 2006; 63(4): 538 - 543. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Lewczuk, G. Beck, H. Esselmann, R. Bruckmoser, R. Zimmermann, M. Fiszer, M. Bibl, J. M. Maler, J. Kornhuber, and J. Wiltfang Effect of Sample Collection Tubes on Cerebrospinal Fluid Concentrations of Tau Proteins and Amyloid {beta} Peptides Clin. Chem., February 1, 2006; 52(2): 332 - 334. [Full Text] [PDF]
|
|
|
|
 |
|
 K. Rostasy, E. Withut, D. Pohl, P. Lange, B. Ciesielcyk, R. Diem, J. Gartner, and M. Otto Tau, Phospho-Tau, and S-100B in the Cerebrospinal Fluid of Children With Multiple Sclerosis J Child Neurol, October 1, 2005; 20(10): 822 - 825. [Abstract] [PDF]
|
|
|
|
|
|
S.-K. Herukka, M. Hallikainen, H. Soininen, and T. Pirttila CSF A{beta}42 and tau or phosphorylated tau and prediction of progressive mild cognitive impairment Neurology, April 12, 2005; 64(7): 1294 - 1297. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Georganopoulou, L. Chang, J.-M. Nam, C. S. Thaxton, E. J. Mufson, W. L. Klein, and C. A. Mirkin From The Cover: Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer's disease PNAS, February 15, 2005; 102(7): 2273 - 2276. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Olsson, H. Vanderstichele, N. Andreasen, G. De Meyer, A. Wallin, B. Holmberg, L. Rosengren, E. Vanmechelen, and K. Blennow Simultaneous Measurement of {beta}-Amyloid(1-42), Total Tau, and Phosphorylated Tau (Thr181) in Cerebrospinal Fluid by the xMAP Technology Clin. Chem., February 1, 2005; 51(2): 336 - 345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S.M. Schoonenboom, C. Mulder, H. Vanderstichele, E.-J. Van Elk, A. Kok, G. J. Van Kamp, P. Scheltens, and M. A. Blankenstein Effects of Processing and Storage Conditions on Amyloid {beta} (1-42) and Tau Concentrations in Cerebrospinal Fluid: Implications for Use in Clinical Practice Clin. Chem., January 1, 2005; 51(1): 189 - 195. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Prince, H. Zetterberg, N. Andreasen, J. Marcusson, and K. Blennow APOE {epsilon}4 allele is associated with reduced cerebrospinal fluid levels of A{beta}42 Neurology, June 8, 2004; 62(11): 2116 - 2118. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. S.M. Schoonenboom, Y. A.L. Pijnenburg, C. Mulder, S. M. Rosso, E. -J. Van Elk, G. J. Van Kamp, J. C. Van Swieten, and Ph. Scheltens Amyloid {beta}(1-42) and phosphorylated tau in CSF as markers for early-onset Alzheimer disease Neurology, May 11, 2004; 62(9): 1580 - 1584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. S. Knopman, B. F. Boeve, and R. C. Petersen Essentials of the Proper Diagnoses of Mild Cognitive Impairment, Dementia, and Major Subtypes of Dementia Mayo Clin. Proc., October 1, 2003; 78(10): 1290 - 1308. [Abstract] [PDF]
|
|
|
|
|
|
D. Galasko Cerebrospinal Fluid Biomarkers in Alzheimer Disease: A Fractional Improvement? Arch Neurol, September 1, 2003; 60(9): 1195 - 1196. [Full Text] [PDF]
|
|
|
|
|
|
A. Maddalena, A. Papassotiropoulos, B. Muller-Tillmanns, H. H. Jung, T. Hegi, R. M. Nitsch, and C. Hock Biochemical Diagnosis of Alzheimer Disease by Measuring the Cerebrospinal Fluid Ratio of Phosphorylated tau Protein to {beta}-Amyloid Peptide42 Arch Neurol, September 1, 2003; 60(9): 1202 - 1206. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Franz, R. Beer, A. Kampfl, K. Engelhardt, E. Schmutzhard, H. Ulmer, and F. Deisenhammer Amyloid beta 1-42 and tau in cerebrospinal fluid after severe traumatic brain injury Neurology, May 13, 2003; 60(9): 1457 - 1461. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Sunderland, G. Linker, N. Mirza, K. T. Putnam, D. L. Friedman, L. H. Kimmel, J. Bergeson, G. J. Manetti, M. Zimmermann, B. Tang, et al. Decreased {beta}-Amyloid1-42 and Increased Tau Levels in Cerebrospinal Fluid of Patients With Alzheimer Disease JAMA, April 23, 2003; 289(16): 2094 - 2103. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. M. Thompson, K. M. Hayashi, G. de Zubicaray, A. L. Janke, S. E. Rose, J. Semple, D. Herman, M. S. Hong, S. S. Dittmer, D. M. Doddrell, et al. Dynamics of Gray Matter Loss in Alzheimer's Disease J. Neurosci., February 1, 2003; 23(3): 994 - 1005. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Riemenschneider, N. Lautenschlager, S. Wagenpfeil, J. Diehl, A. Drzezga, and A. Kurz Cerebrospinal Fluid Tau and {beta}-Amyloid 42 Proteins Identify Alzheimer Disease in Subjects With Mild Cognitive Impairment Arch Neurol, November 1, 2002; 59(11): 1729 - 1734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. D. Silverberg, E. Levinthal, E. V. Sullivan, D. A. Bloch, S. D. Chang, J. Leverenz, S. Flitman, R. Winn, F. Marciano, T. Saul, et al. Assessment of low-flow CSF drainage as a treatment for AD: Results of a randomized pilot study Neurology, October 22, 2002; 59(8): 1139 - 1145. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Fassbender, M. Stroick, T. Bertsch, A. Ragoschke, S. Kuehl, S. Walter, J. Walter, K. Brechtel, F. Muehlhauser, K. von Bergmann, et al. Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide Neurology, October 22, 2002; 59(8): 1257 - 1258. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Delacourte, N. Sergeant, D. Champain, A. Wattez, C.-A. Maurage, F. Lebert, F. Pasquier, and J.-P. David Nonoverlapping but synergetic tau and APP pathologies in sporadic Alzheimer's disease Neurology, August 13, 2002; 59(3): 398 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Buerger, R. Zinkowski, S. J. Teipel, T. Tapiola, H. Arai, K. Blennow, N. Andreasen, K. Hofmann-Kiefer, J. DeBernardis, D. Kerkman, et al. Differential Diagnosis of Alzheimer Disease With Cerebrospinal Fluid Levels of Tau Protein Phosphorylated at Threonine 231 Arch Neurol, August 1, 2002; 59(8): 1267 - 1272. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Riemenschneider, S. Wagenpfeil, J. Diehl, N. Lautenschlager, T. Theml, B. Heldmann, A. Drzezga, T. Jahn, H. Forstl, and A. Kurz Tau and A{beta}42 protein in CSF of patients with frontotemporal degeneration Neurology, June 11, 2002; 58(11): 1622 - 1628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Y. Hu, S. S. He, X. Wang, Q. H. Duan, I. Grundke-Iqbal, K. Iqbal, and J. Wang Levels of Nonphosphorylated and Phosphorylated Tau in Cerebrospinal Fluid of Alzheimer's Disease Patients : An Ultrasensitive Bienzyme-Substrate-Recycle Enzyme-Linked Immunosorbent Assay Am. J. Pathol., April 1, 2002; 160(4): 1269 - 1278. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Otto, J. Wiltfang, L. Cepek, M. Neumann, B. Mollenhauer, P. Steinacker, B. Ciesielczyk, W. Schulz-Schaeffer, H. A. Kretzschmar, and S. Poser Tau protein and 14-3-3 protein in the differential diagnosis of Creutzfeldt-Jakob disease Neurology, January 22, 2002; 58(2): 192 - 197. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Padovani, B. Borroni, F. Colciaghi, C. Pettenati, E. Cottini, C. Agosti, G. L. Lenzi, C. Caltagirone, M. Trabucchi, F. Cattabeni, et al. Abnormalities in the Pattern of Platelet Amyloid Precursor Protein Forms in Patients With Mild Cognitive Impairment and Alzheimer Disease Arch Neurol, January 1, 2002; 59(1): 71 - 75. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Padovani, L. Pastorino, B. Borroni, F. Colciaghi, L. Rozzini, R. Monastero, J. Perez, C. Pettenati, M. Mussi, G. Parrinello, et al. Amyloid precursor protein in platelets: A peripheral marker for the diagnosis of sporadic AD Neurology, December 26, 2001; 57(12): 2243 - 2248. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Sjogren, H. Vanderstichele, H. Agren, O. Zachrisson, M. Edsbagge, C. Wikkelso, I. Skoog, A. Wallin, L.-O. Wahlund, J. Marcusson, et al. Tau and A{beta}42 in Cerebrospinal Fluid from Healthy Adults 21-93 Years of Age: Establishment of Reference Values Clin. Chem., October 1, 2001; 47(10): 1776 - 1781. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E Kapaki, K Kilidireas, G P Paraskevas, M Michalopoulou, and E Patsouris Highly increased CSF tau protein and decreased {beta}-amyloid (1-42) in sporadic CJD: a discrimination from Alzheimer's disease? J. Neurol. Neurosurg. Psychiatry, September 1, 2001; 71(3): 401 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. S. Knopman, S. T. DeKosky, J. L. Cummings, H. Chui, J. Corey-Bloom, N. Relkin, G. W. Small, B. Miller, and J. C. Stevens Practice parameter: Diagnosis of dementia (an evidence-based review): Report of the Quality Standards Subcommittee of the American Academy of Neurology Neurology, May 8, 2001; 56(9): 1143 - 1153. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Knopman Cerebrospinal Fluid {beta}-Amyloid and Tau Proteins for the Diagnosis of Alzheimer Disease Arch Neurol, March 1, 2001; 58(3): 349 - 350. [Full Text] [PDF]
|
|
|
|
|
|
R. Diaz-Arrastia and F. Baskin New Biochemical Markers in Alzheimer Disease Arch Neurol, March 1, 2001; 58(3): 354 - 356. [Full Text] [PDF]
|
|
|
|
|
|
N. Andreasen, L. Minthon, P. Davidsson, E. Vanmechelen, H. Vanderstichele, B. Winblad, and K. Blennow Evaluation of CSF-tau and CSF-A{beta}42 as Diagnostic Markers for Alzheimer Disease in Clinical Practice Arch Neurol, March 1, 2001; 58(3): 373 - 379. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Kanemaru, N. Kameda, and H. Yamanouchi Decreased CSF amyloid {beta}42 and normal tau levels in dementia with Lewy bodies Neurology, May 9, 2000; 54(9): 1875 - 1876. [Full Text] [PDF]
|
|
|
|
|
|
M. Otto, H. Esselmann, W. Schulz-Schaeffer, M. Neumann, A. Schroter, P. Ratzka, L. Cepek, I. Zerr, P. Steinacker, O. Windl, et al. Decreased {beta}-amyloid1-42 in cerebrospinal fluid of patients with Creutzfeldt-Jakob disease Neurology, March 14, 2000; 54(5): 1099 - 1102. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. A. Kaye Methods for Discerning Disease-Modifying Effects in Alzheimer Disease Treatment Trials Arch Neurol, March 1, 2000; 57(3): 312 - 314. [Full Text] [PDF]
|
|
|
|
|
|
P. D. Mehta, T. Pirttila, S. P. Mehta, E. A. Sersen, P. S. Aisen, and H. M. Wisniewski Plasma and Cerebrospinal Fluid Levels of Amyloid {beta} Proteins 1-40 and 1-42 in Alzheimer Disease Arch Neurol, January 1, 2000; 57(1): 100 - 105. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Advances in Diagnosing and Predicting the Progression of AD Journal Watch Psychiatry, August 1, 1999; 1999(801): 11 - 11. [Full Text]
|
|
|
|
|
|
S. E. Black The search for diagnostic and progression markers in AD Neurology, May 1, 1999; 52(8): 1533 - 1533. [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
