Value of CSF β-amyloid1–42 and tau as predictors of Alzheimer's disease in patients with mild cognitive impairment
Abstract
Subjects with mild cognitive impairment (MCI) are at a high risk of developing clinical Alzheimer's disease (AD). We asked to what extent the core biomarker candidates cerebro-spinal fluid (CSF) beta-amyloid(1-42) (Abeta(1-42)) and CSF tau protein concentrations predict conversion from MCI to AD. We studied 52 patients with MCI, 93 AD patients, and 10 healthy controls (HC). The MCI group was composed of 29 patients who had converted to AD during follow-up, and of 23 patients who showed no cognitive decline. CSF Abeta(1-42) and tau protein levels were assessed at baseline in all subjects, using enzyme-linked immunosorbent assays. For assessment of sensitivity and specificity, we used independently established reference values for CSF Abeta(1-42) and CSF tau. The levels of CSF tau were increased, whereas levels of Abeta(1-42) were decreased in MCI subjects. Abeta(1-42) predicted AD in converted MCI with a sensitivity of 59% and a specificity of 100% compared to HC. Tau yielded a greater sensitivity of 83% and a specificity of 90%. In a multiple Cox regression analysis within the MCI group, low baseline levels of Abeta(1-42), but not other predictor variables (tau protein, gender, age, apolipoprotein E epsilon4 carrier status, Mini Mental Status Examination score, observation time, antidementia therapy), correlated with conversion status (P<0.05). Our findings support the notion that CSF tau and Abeta(1-42) may be useful biomarkers in the early identification of AD in MCI subjects.
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In MCI subjects, CSF tau was increased and CSF Aβ1-42 was decreased compared to healthy controls with good comparable accuracy.
“When CSF beta amyloid (CSF Aβ1-42) and tau protein levels were tested in MCI subjects, CSF tau was increased whereas levels of CSF Aβ1–42 were decreased compared to healthy controls with good comparable accuracy.”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [91]
Aβ1-42 and CSF tau showed a sensitivity of 59% and 83% with a specificity of 100% and 90% respectively.
“Aβ1–42 and CSF tau showed a sensitivity of 59% and 83% with a specificity of 100% and 90% respectively [91].”
From Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease (2020) · cites this paper as [91]
Cites
Regression Models and Life-Tables
Cox, D. R. (1972) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1972.tb00899.x · Cited by 39,793 · see citing works
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D., & Stadlan, E. M. (1984) · Neurology · doi:10.1212/wnl.34.7.939 · Cited by 27,915 · see citing works
The Clinical Dementia Rating (CDR): Current version and scoring rules
Morris, J. C. (1993) · Neurology · doi:10.1212/wnl.43.11.2412-a · Cited by 9,882 · see citing works
Mild Cognitive Impairment: Clinical Characterization and Outcome
Petersen, R. C., Smith, G. E., Waring, S. C., Ivnik, R. J., Tangalos, E. G., & Kokmen, E. (1999) · Archives of Neurology · doi:10.1001/archneur.56.3.303 · Cited by 8,980 · see citing works
A new rating scale for Alzheimer's disease
(1984) · American Journal of Psychiatry · doi:10.1176/ajp.141.11.1356 · Cited by 4,175 · see citing works
CSF markers for incipient Alzheimer's disease
Blennow, K., & Hampel, H. (2003) · The Lancet Neurology · doi:10.1016/s1474-4422(03)00530-1 · Cited by 1,291 · see citing works
Self-citationImproved discrimination of AD patients using β-amyloid <sub>(1-42)</sub> and tau levels in CSF
Hulstaert, F., Blennow, K., Ivanoiu, A., Schoonderwaldt, H. C., Riemenschneider, M., Deyn, P. P. D., Bancher, C., Cras, P., Wiltfang, J., Mehta, P. D., et al. (1999) · Neurology · doi:10.1212/wnl.52.8.1555 · Cited by 724 · see citing works
Self-citationMotter, R., Vigo‐Pelfrey, C., Kholodenko, D., Barbour, R., Johnson‐Wood, K., Galasko, D., Chang, L., Miller, B., Clark, C., Green, R., et al. (1995) · Annals of Neurology · doi:10.1002/ana.410380413 · Cited by 701 · see citing works
Andreasen, N., Hesse, C., Davidsson, P., Minthon, L., Wallin, A., Winblad, B., Vanderstichele, H., Vanmechelen, E., & Blennow, K. (1999) · Archives of Neurology · doi:10.1001/archneur.56.6.673 · Cited by 660 · see citing works
Self-citationMorris, J. C., & Price, J. L. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:101 · Cited by 513 · see citing works
Galasko, D., Chang, L., Motter, R., Clark, C. M., Kaye, J., Knopman, D., Thomas, R., Kholodenko, D., Schenk, D., Lieberburg, I., et al. (1998) · Archives of Neurology · doi:10.1001/archneur.55.7.937 · Cited by 442 · see citing works
Sjögren, M., Vanderstichele, H., Ågren, H., Zachrisson, O., Edsbagge, M., Wikkelsø, C., Skoog, I., Wallin, A., Wahlund, L.-O., Marcusson, J., et al. (2001) · Clinical Chemistry · doi:10.1093/clinchem/47.10.1776 · Cited by 436 · see citing works
Self-citationHampel, H., Buerger, K., Zinkowski, R., Teipel, S. J., Goernitz, A., Andreasen, N., Sjoegren, M., DeBernardis, J., Kerkman, D., Ishiguro, K., et al. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.1.95 · Cited by 434 · see citing works
Self-citationKanai, M., Matsubara, E., Isoe, K., Urakami, K., Nakashima, K., Arai, H., Sasaki, H., Abe, K., Iwatsubo, T., Kosaka, T., et al. (1998) · Annals of Neurology · doi:10.1002/ana.410440108 · Cited by 340 · see citing works
CSF Total tau, Aβ42 and Phosphorylated tau Protein as Biomarkers for Alzheimer's Disease
Blennow, K., Vanmechelen, E., & Hampel, H. J. (2001) · Molecular Neurobiology · doi:10.1385/mn:24:1-3:087 · Cited by 263 · see citing works
Self-citationCSF tau protein phosphorylated at threonine 231 correlates with cognitive decline in MCI subjects
Büerger, K., Teipel, S. J., Zinkowski, R. P., Blennow, K., Arai, H., Engel, R. R., Hofmann‐Kiefer, K., McCulloch, C., Ptok, U., Heun, R., et al. (2002) · Neurology · doi:10.1212/wnl.59.4.627 · Cited by 255 · see citing works
Self-citationBiological markers for therapeutic trials in Alzheimer’s disease
Frank, R., Galasko, D., Hampel, H. J., Hardy, J., de Leon, M. J., Mehta, P. D., Rogers, J., Siemers, E., & Trojanowski, J. Q. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(03)00002-2 · Cited by 252 · see citing works
Self-citationSchofield, P. W., Marder, K. S., Dooneief, G., Jacobs, D. M., & Sano, M. C. (1997) · American Journal of Psychiatry · doi:10.1176/ajp.154.5.609 · Cited by 239 · see citing works
Sjögren, M. J. C., Minthon, L., Davidsson, P., Granérus, A., Clarberg, A., Vanderstichele, H., Vanmechelen, E., Wallin, A., & Blennow, K. (2000) · Journal of Neural Transmission · doi:10.1007/s007020070079 · Cited by 237 · see citing works
Self-citationAndreasen, N. C., Minthon, L., Vanmechelen, E., Vanderstichele, H., Davidsson, P., Winblad, B. G., & Blennow, K. (1999) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00617-5 · Cited by 236 · see citing works
Self-citationCombination assay of CSF Tau, Aβ1-40 and Aβ1-42(43) as a biochemical marker of Alzheimer's disease
Shoji, M., Matsubara, E., Kanai, M., Watanabe, M., Nakamura, T., Tomidokoro, Y., Shizuka, M., Wakabayashi, K., Igeta, Y., Ikeda, Y., et al. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00122-1 · Cited by 219 · see citing works
Riemenschneider, M. J., Lautenschlager, N. T., Wagenpfeil, S., Diehl, J., Drzezga, A. E., & Kurz, A. (2002) · Archives of Neurology · doi:10.1001/archneur.59.11.1729 · Cited by 212 · see citing works
Assessment of CSF levels of tau protein in mildly demented patients with Alzheimer's disease
Galasko, D. R., Clark, C., Chang, L., Miller, B. L., Green, R. C., Motter, R. N., & Seubert, P. A. (1997) · Neurology · doi:10.1212/wnl.48.3.632 · Cited by 153 · see citing works
A Longitudinal Study of Cognitive Function in Elderly Persons with Subjective Memory Complaints
Flicker, C., Ferris, S. H., & Reisberg, . (1993) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1993.tb06448.x · Cited by 142 · see citing works
Amyloid β protein 42(43) in cerebrospinal fluid of patients with Alzheimer's disease
Tamaoka, A., Sawamura, N., Fukushima, T., Shoji, S., Matsubara, E., Shoji, M., Hirai, S., Furiya, Y., Endoh, R., & Mori, H. (1997) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(96)00314-0 · Cited by 139 · see citing works
Increased cerebrospinal fluid tau in patients with Alzheimer's disease
Jensen, M., Basun, H., & Lannfelt, L. (1995) · Neuroscience Letters · doi:10.1016/0304-3940(95)11297-a · Cited by 131 · see citing works
CSF Phosphorylated Tau Protein and Mild Cognitive Impairment: A Prospective Study
Arai, H., Ishiguro, K., Ohno, H., Moriyama, M., Itoh, N., Okamura, N., Matsui, T., Morikawa, Y.-I., Horikawa, E., Kohno, H., et al. (2000) · Experimental Neurology · doi:10.1006/exnr.2000.7501 · Cited by 123 · see citing works
Maruyama, M., Arai, H., Sugita, M., Tanji, H., Higuchi, M., Okamura, N., Matsui, T., Higuchi, S., Matsushita, S., Yoshida, H., et al. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7814 · Cited by 97 · see citing works
Cerebrospinal protein tau is elevated in early Alzheimer's disease
Riemenschneider, M. J., Buch, K., Schmolke, M., Kurz, A., & Guder, W. G. (1996) · Neuroscience Letters · doi:10.1016/0304-3940(96)12810-x · Cited by 90 · see citing works
Hampel, H. J., Goernitz, A., & Büerger, K. (2003) · Brain Research Bulletin · doi:10.1016/s0361-9230(03)00087-x · Cited by 88 · see citing works
Self-citationRiemenschneider, M. J., Schmolke, M., Lautenschlager, N. T., Guder, W. G., Vanderstichele, H., Vanmechelen, E., & Kurz, A. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(00)00976-9 · Cited by 84 · see citing works
Harwood (2001) · doi:10.1002/1099-1166(200102)16:2
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Advancing research diagnostic criteria for Alzheimer's disease: the IWG-2 criteria
Dubois, B., Feldman, H. H., Jacova, C., Hampel, H., Molinuevo, J. L., Blennow, K., DeKosky, S. T., Gauthier, S., Selkoe, D., Bateman, R., et al. (2014) · The Lancet Neurology · doi:10.1016/s1474-4422(14)70090-0 · Cited by 3,321 · see citing works
Self-citationHansson, O., Zetterberg, H., Buchhave, P., Londos, E., Blennow, K., & Minthon, L. (2006) · The Lancet Neurology · doi:10.1016/s1474-4422(06)70355-6 · Cited by 1,700 · see citing works
Self-citationMitchell, A. J., & Shiri‐Feshki, M. (2009) · Acta Psychiatrica Scandinavica · doi:10.1111/j.1600-0447.2008.01326.x · Cited by 1,659 · see citing works
CSF Biomarkers and Incipient Alzheimer Disease in Patients With Mild Cognitive Impairment
Mattsson, N. (2009) · JAMA · doi:10.1001/jama.2009.1064 · Cited by 1,176 · see citing works
Fagan, A. M., Roe, C. M., Xiong, C., Mintun, M. A., Morris, J. C., & Holtzman, D. M. (2007) · Archives of Neurology · doi:10.1001/archneur.64.3.noc60123 · Cited by 897 · see citing works
Recent Advancements in Pathogenesis, Diagnostics and Treatment of Alzheimer’s Disease
Khan, S., Barve, K. H., & Kumar, M. S. (2020) · Current Neuropharmacology · doi:10.2174/1570159x18666200528142429 · Cited by 820 · see citing works
“Aβ1–42 and CSF tau showed a sensitivity of 59% and 83% with a specificity of 100% and 90% respectively [91].”
BackgroundTotal and phosphorylated tau protein as biological markers of Alzheimer’s disease
Hampel, H., Blennow, K., Shaw, L. M., Hoessler, Y. C., Zetterberg, H., & Trojanowski, J. Q. (2010) · Experimental Gerontology · doi:10.1016/j.exger.2009.10.010 · Cited by 389 · see citing works
Self-citationIntraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease
Gouras, G. K., Tampellini, D., Takahashi, R. H., & Capetillo-Zarate, E. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0679-9 · Cited by 372 · see citing works
Grimmer, T., Riemenschneider, M., Förstl, H., Henriksen, G., Klunk, W. E., Mathis, C. A., Shiga, T., Wester, H.-J., Kurz, A., & Drzezga, A. (2009) · Biological Psychiatry · doi:10.1016/j.biopsych.2009.01.027 · Cited by 278 · see citing works
Hampel, H., Hu, Y., Cummings, J., Mattke, S., Iwatsubo, T., Nakamura, A., Vellas, B., O’Bryant, S., Shaw, L. M., Cho, M., et al. (2023) · Neuron · doi:10.1016/j.neuron.2023.05.017 · Cited by 283 · see citing works
Self-citationAssociation of Amyloid Pathology With Myelin Alteration in Preclinical Alzheimer Disease
Dean, D. C., Hurley, S. A., Kecskemeti, S. R., O’Grady, J. P., Canda, C., Davenport-Sis, N. J., Carlsson, C. M., Zetterberg, H., Blennow, K., Asthana, S., et al. (2017) · JAMA Neurology · doi:10.1001/jamaneurol.2016.3232 · Cited by 252 · see citing works
Self-citationMielke, M. M., Frank, R. D., Dage, J. L., Jeromin, A., Ashton, N. J., Blennow, K., Karikari, T. K., Vanmechelen, E., Zetterberg, H., Algeciras-Schimnich, A., et al. (2021) · JAMA Neurology · doi:10.1001/jamaneurol.2021.2293 · Cited by 244 · see citing works
Self-citationZhong, Z., Ewers, M., Teipel, S., Bürger, K., Wallin, A., Blennow, K., He, P., McAllister, C., Hampel, H., & Shen, Y. (2007) · Archives of General Psychiatry · doi:10.1001/archpsyc.64.6.718 · Cited by 206 · see citing works
Self-citationCerebrospinal Fluid Biomarkers of Neurovascular Dysfunction in Mild Dementia and Alzheimer'S Disease
Sweeney, M. D., Sagare, A. P., & Zlokovic, B. V. (2015) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2015.76 · Cited by 122 · see citing works
Propagation of Tau via Extracellular Vesicles
Pérez, M., Avila, J., & Hernández, F. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2019.00698 · Cited by 118 · see citing works
Ewers, M., Zhong, Z., Bürger, K., Wallin, A., Blennow, K., Teipel, S. J., Shen, Y., & Hampel, H. (2008) · Brain · doi:10.1093/brain/awn034 · Cited by 119 · see citing works
Self-citationYaribeygi, H., Rashidy-Pour, A., Atkin, S. L., Jamialahmadi, T., & Sahebkar, A. (2021) · Life Sciences · doi:10.1016/j.lfs.2020.118645 · Cited by 96 · see citing works
Bendlin, B. B., Carlsson, C. M., Johnson, S. C., Zetterberg, H., Blennow, K., Willette, A. A., Okonkwo, O. C., Sodhi, A., Ries, M. L., Birdsill, A. C., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0037720 · Cited by 91 · see citing works
Self-citationKauwe, J. S. K., Jacquart, S., Chakraverty, S., Wang, J., Mayo, K., Fagan, A. M., Holtzman, D. M., Morris, J. C., & Goate, A. M. (2007) · Annals of Neurology · doi:10.1002/ana.21099 · Cited by 84 · see citing works
The application of cerebrospinal fluid biomarkers in early diagnosis of Alzheimer disease
Blennow, K., & Zetterberg, H. (2013) · Medical Clinics of North America · doi:10.1016/j.mcna.2012.12.012 · Cited by 69 · see citing works
Self-citationIncreased CSF-BACE1 activity associated with decreased hippocampus volume in Alzheimer’s disease
Ewers, M., Cheng, X., Zhong, Z., Nural, H. F., Walsh, C., Meindl, T., Teipel, S. J., Buerger, K., He, P., Shen, Y., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2011-091153 · Cited by 58 · see citing works
Self-citationAssociations between white matter lesions, cerebrovascular risk factors, and low CSF Aβ42
Stenset, V., Johnsen, L., Kocot, D., Negaard, A., Skinningsrud, A., Gulbrandsen, P., Wallin, A., & Fladby, T. (2006) · Neurology · doi:10.1212/01.wnl.0000234030.77831.5a · Cited by 44 · see citing works
Llano, D. A., Devanarayan, P., & Devanarayan, V. (2019) · Alzheimer Disease & Associated Disorders · doi:10.1097/wad.0000000000000328 · Cited by 35 · see citing works
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Sabbagh, J. J., Kinney, J. W., & Cummings, J. L. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.04.010 · Cited by 27 · see citing works
Schjønning Nielsen, M., Simonsen, A. H., Siersma, V., Engedal, K., Jelic, V., Andersen, B. B., Naik, M., Hasselbalch, S. G., & Høgh, P. (2018) · Dementia and Geriatric Cognitive Disorders Extra · doi:10.1159/000490788 · Cited by 15 · see citing works
- Authors
- Hampel, H., Teipel, S. J., Fuchsberger, T., Andreasen, N., Wiltfang, J., Otto, M., Shen, Y., Dodel, R., Du, Y., Farlow, M., Möller, H.-J., Blennow, K., & Buerger, K.
- Affiliations
- Ludwig-Maximilians-Universität München (DE)
- Karolinska Institutet (SE)
- Friedrich-Alexander-Universität Erlangen-Nürnberg (DE)
- University of Göttingen (DE)
- Banner Sun Health Research Institute (US)
- University of Bonn (DE)
- Indiana University School of Medicine (US)
- Sahlgrenska University Hospital (SE)
- ORCID
- Venue
- Molecular Psychiatry
- Published
- 2003-12-30
- Volume
- 9
- Issue
- 7
- Pages
- 705-710
- ISSN
- 1359-4184 (ISSN-L)
- 1476-5578
- OpenAlex
- W2000816306
- Cited by
- 287
- References
- 33
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 8 · 2023: 6 · 2022: 6 · 2021: 7 · 2020: 14 · 2019: 10 · 2018: 7 · 2017: 9 · 2016: 5 · 2015: 15 · 2014: 12 · 2013: 17 · 2012: 17
- FWCI
- 7.55
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Molecular Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Cancer-related cognitive impairment studies
- Keywords
- Alzheimer's disease, mild cognitive impairment, cerebrospinal fluid, amyloid-beta 42, tau protein, biomarkers, conversion to Alzheimer's disease, early diagnosis, APOE ε4
- MeSH terms
- Aged, Aged, 80 and over, Alzheimer Disease, Apolipoproteins E, Cognition Disorders, Female, Humans, Male, Middle Aged, Peptide Fragments, Predictive Value of Tests, Prognosis, Sensitivity and Specificity, Severity of Illness Index, Biomarkers, Proportional Hazards Models, Amyloid beta-Peptides, tau Proteins, Apolipoprotein E4
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