Decreased β-Amyloid1-42and Increased Tau Levels in Cerebrospinal Fluid of Patients With Alzheimer Disease
Abstract
Context Alzheimer disease (AD) is characterized by pathological results at autopsy of amyloid plaques and tau-associated neurofibrillary tangles, but the clinical diagnosis of AD is determined on the basis of medical history, cognitive symptoms, and exclusionary criteria. The search for antemortem biomarkers is intense and has focused on cerebrospinal fluid (CSF) beta-amyloid1-42 and tau proteins. Objectives To compare CSF beta-amyloid and tau levels in a new population of AD patients and controls. To perform a meta-analysis of studies of CSF beta-amyloid and tau levels in AD patients and controls. Design Cross-sectional study of the comparison of baseline CSF beta-amyloid1-42 and tau levels in AD patients and controls. Meta-analysis involved 17 studies of CSF beta-amyloid and 34 studies of CSF tau. Setting Clinical research unit of the National Institute of Mental Health, Bethesda, Md. Patients The Geriatric Psychiatry Branch evaluated AD patients as inpatients at the National Institutes of Health Clinical Center between May 1985 and January 2001. A total of 203 patients participated in this study (131 with AD and 72 controls). None had other serious illnesses, and 31 of 131 AD cases had AD confirmed at autopsy. Meta-analysis provided an additional 3133 AD patients and 1481 controls. Main outcome measures Levels of CSF beta-amyloid1-42 were measured by a sandwich enzyme-linked immunoabsorbent assay with a polyclonal capture antibody and a monoclonal detection antibody. Level…
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Low concentrations of Aβ42 in the CSF reflect the presence of cerebral Aβ deposition, likely as a result of Aβ42 being sequestered into amyloid plaques, changing the equilibrium between the brain and CSF pools of Aβ.
“low concentrations of Aβ42 in the cerebrospinal fluid (CSF) reflect the presence of cerebral Aβ deposition, likely as a result of Aβ42 being sequestered into amyloid plaques, changing the equilibrium between the brain and CSF pools of Aβ (20-22).”
From Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance (2011) · cites this paper as [20]
CSF Aβ42 levels are typically reduced in dementia of the Alzheimer type (DAT), reflecting its aggregation and deposition as amyloid in the brain.
“Levels of CSF Aβ42 are typically reduced in dementia of the Alzheimer type (DAT),8-11 reflecting its aggregation and deposition as amyloid in the brain,12”
From Decreased cerebrospinal fluid Aβ <sub>42</sub> correlates with brain atrophy in cognitively normal elderly (2009) · cites this paper as [8]
Cites
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975) · Journal of Psychiatric Research · doi:10.1016/0022-3956(75)90026-6 · Cited by 88,282 · 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
Itoh, N., Arai, H., Urakami, K., Ishiguro, K., Ohno, H., Hampel, H., Buerger, K., Wiltfang, J., Otto, M., Kretzschmar, H., et al. (2001) · Annals of Neurology · doi:10.1002/ana.1054 · Cited by 256 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Blennow, K., de Leon, M. J., & Zetterberg, H. (2006) · The Lancet · doi:10.1016/s0140-6736(06)69113-7 · Cited by 3,134 · see citing works
Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects
Shaw, L. M., Vanderstichele, H., Knapik‐Czajka, M., Clark, C. M., Aisen, P. S., Petersen, R. C., Blennow, K., Soares, H., Simon, A., Lewczuk, P., et al. (2009) · Annals of Neurology · doi:10.1002/ana.21610 · Cited by 2,065 · see citing works
Cerebrospinal fluid and plasma biomarkers in Alzheimer disease
Blennow, K., Hampel, H., Weiner, M., & Zetterberg, H. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.4 · Cited by 1,863 · 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
Human ApoE isoforms differentially regulate brain amyloid-β peptide clearance
Castellano, J. M., Kim, J., Stewart, F. R., Jiang, H., DeMattos, R. B., Patterson, B. W., Fagan, A. M., Morris, J. C., Mawuenyega, K. G., Cruchaga, C., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002156 · Cited by 1,227 · see citing works
“In particular, low concentrations of Aβ42 in the cerebrospinal fluid (CSF) reflect the presence of cerebral Aβ deposition, likely as a result of Aβ42 being sequestered into amyloid plaques, changing the equilibrium between the brain and CSF pools of Aβ (20-22).”
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
<i>APOE</i> predicts amyloid‐beta but not tau Alzheimer pathology in cognitively normal aging
Morris, J. C., Roe, C. M., Xiong, C., Fagan, A. M., Goate, A. M., Holtzman, D. M., & Mintun, M. A. (2010) · Annals of Neurology · doi:10.1002/ana.21843 · Cited by 830 · see citing works
Georganopoulou, D. G., Chang, L., Nam, J.-M., Thaxton, C. S., Mufson, E. J., Klein, W. L., & Mirkin, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409336102 · Cited by 835 · see citing works
Multimodal techniques for diagnosis and prognosis of Alzheimer's disease
Perrin, R. J., Fagan, A. M., & Holtzman, D. M. (2009) · Nature · doi:10.1038/nature08538 · Cited by 702 · see citing works
Xia, C., Arteaga, J., Chen, G., Gangadharmath, U., Gomez, L. F., Kasi, D., Lam, C., Liang, Q., Liu, C., Mocharla, V. P., et al. (2013) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2012.11.008 · Cited by 605 · see citing works
At the interface of sensory and motor dysfunctions and Alzheimer’s disease.
Albers, M. W., Gilmore, G. C., Kaye, J., Murphy, C., Wingfield, A., Bennett, D. A., Boxer, A. L., Buchman, A. S., Cruickshanks, K. J., Devanand, D. P., et al. (2015) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2014.04.514 · Cited by 589 · see citing works
YKL-40: A Novel Prognostic Fluid Biomarker for Preclinical Alzheimer's Disease
Craig-Schapiro, R., Perrin, R. J., Roe, C. M., Xiong, C., Carter, D., Cairns, N. J., Mintun, M. A., Peskind, E. R., Li, G., Galasko, D. R., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.025 · Cited by 504 · see citing works
Morris, J. C., Roe, C. M., Grant, E. A., Head, D., Storandt, M., Goate, A. M., Fagan, A. M., Holtzman, D. M., & Mintun, M. A. (2009) · Archives of Neurology · doi:10.1001/archneurol.2009.269 · Cited by 476 · see citing works
Longitudinal Change in CSF Biomarkers in Autosomal-Dominant Alzheimer’s Disease
Fagan, A. M., Xiong, C., Jasielec, M. S., Bateman, R. J., Goate, A. M., Benzinger, T. L. S., Ghetti, B., Martins, R. N., Masters, C. L., Mayeux, R., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3007901 · Cited by 434 · see citing works
GWAS of Cerebrospinal Fluid Tau Levels Identifies Risk Variants for Alzheimer’s Disease
Cruchaga, C., Kauwe, J. S. K., Harari, O., Jin, S. C., Cai, Y., Karch, C. M., Benitez, B. A., Jeng, A. T., Skorupa, T., Carrell, D., et al. (2013) · Neuron · doi:10.1016/j.neuron.2013.02.026 · Cited by 383 · see citing works
The inter-relationship between delirium and dementia: the importance of delirium prevention
Fong, T. G., & Inouye, S. K. (2022) · Nature Reviews Neurology · doi:10.1038/s41582-022-00698-7 · Cited by 404 · see citing works
Goldman, J. S., Hahn, S. E., Catania, J. W., Larusse-Eckert, S., Butson, M. B., Rumbaugh, M., Strecker, M. N., Roberts, J. S., Burke, W., Mayeux, R., et al. (2011) · Genetics in Medicine · doi:10.1097/gim.0b013e31821d69b8 · Cited by 393 · see citing works
Total 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
del Campo, M., Mollenhauer, B., Bertolotto, A., Engelborghs, S., Hampel, H., Simonsen, A. H., Kapaki, E., Kruse, N., Le Bastard, N., Lehmann, S., et al. (2012) · Biomarkers in Medicine · doi:10.2217/bmm.12.46 · Cited by 343 · see citing works
Vanderstichele, H., Bibl, M., Engelborghs, S., Le Bastard, N., Lewczuk, P., Molinuevo, J. L., Parnetti, L., Perret‐Liaudet, A., Shaw, L. M., Teunissen, C., et al. (2012) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2011.07.004 · Cited by 358 · see citing works
Fagan, A. M., Head, D., Shah, A. R., Marcus, D., Mintun, M., Morris, J. C., & Holtzman, D. M. (2009) · Annals of Neurology · doi:10.1002/ana.21559 · Cited by 327 · see citing works
A systematic review of neurotransmitter deficits and treatments in frontotemporal dementia
Huey, E. D., Putnam, K. T., & Grafman, J. (2006) · Neurology · doi:10.1212/01.wnl.0000191304.55196.4d · Cited by 299 · see citing works
Self-citationRetinal vascular biomarkers for early detection and monitoring of Alzheimer’s disease
Frost, S., Kanagasingam, Y., Sohrabi, H., Vignarajan, J., Bourgeat, P., Salvado, O., Villemagne, V, Rowe, C. C., Lance Macaulay, S., Szoeke, C., et al. (2013) · Translational Psychiatry · doi:10.1038/tp.2012.150 · Cited by 297 · 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
Laske, C., Stransky, E., Leyhe, T., Eschweiler, G. W., Maetzler, W., Wittorf, A., Soekadar, S., Richartz, E., Koehler, N., Bartels, M., et al. (2007) · Journal of Psychiatric Research · doi:10.1016/j.jpsychires.2006.01.014 · Cited by 272 · see citing works
High‐molecular‐weight β‐amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients
Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., & Nakagawa, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-150359 · Cited by 264 · see citing works
Fluctuations of CSF amyloid-β levels: Implications for a diagnostic and therapeutic biomarker
Bateman, R. J., Wen, G., Morris, J. C., & Holtzman, D. M. (2007) · Neurology · doi:10.1212/01.wnl.0000256043.50901.e3 · Cited by 260 · see citing works
Scherling, C. S., Hall, T., Berisha, F., Klepac, K., Karydas, A., Coppola, G., Kramer, J. H., Rabinovici, G., Ahlijanian, M., Miller, B. L., et al. (2014) · Annals of Neurology · doi:10.1002/ana.24052 · Cited by 249 · see citing works
Mosconi, L., De Santi, S., Brys, M., Tsui, W. H., Pirraglia, E., Glodzik-Sobanska, L., Rich, K. E., Switalski, R., Mehta, P. D., Pratico, D., et al. (2008) · Biological Psychiatry · doi:10.1016/j.biopsych.2007.05.030 · Cited by 238 · see citing works
(ADNI), A. D. N. I., Deming, Y., The Alzheimer Disease Genetic Consortium (ADGC), Li, Z., Kapoor, M., Harari, O., Del-Aguila, J. L., Black, K., Carrell, D., Cai, Y., et al. (2017) · Acta Neuropathologica · doi:10.1007/s00401-017-1685-y · Cited by 231 · see citing works
Biomarkers for the Early Detection and Progression of Alzheimer's Disease
Counts, S. E., Ikonomovic, M. D., Mercado, N., Vega, I. E., & Mufson, E. J. (2017) · Neurotherapeutics · doi:10.1007/s13311-016-0481-z · Cited by 224 · see citing works
Fluid Biomarkers in Alzheimer Disease
Blennow, K., Zetterberg, H., & Fagan, A. M. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006221 · Cited by 208 · see citing works
Biochemical markers in persons with preclinical familial Alzheimer disease
Ringman, J. M., Younkin, S. G., Pratico, D., Seltzer, W., Cole, G. M., Geschwind, D. H., Rodriguez-Agudelo, Y., Schaffer, B., Fein, J., Sokolow, S., et al. (2008) · Neurology · doi:10.1212/01.wnl.0000303973.71803.81 · Cited by 198 · see citing works
Molecular diagnostics of neurodegenerative disorders
Agrawal, M., & Biswas, A. (2015) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2015.00054 · Cited by 164 · see citing works
Spellman, D. S., Wildsmith, K. R., Honigberg, L. A., Tuefferd, M., Baker, D., Raghavan, N., Nairn, A. C., Croteau, P., Schirm, M., Allard, R., et al. (2015) · PROTEOMICS – Clinical Applications · doi:10.1002/prca.201400178 · Cited by 161 · see citing works
Biomarkers used in Alzheimer’s disease diagnosis, treatment, and prevention
Mahaman, Y. A. R., Embaye, K. S., Huang, F., Li, L., Zhu, F., Wang, J.-Z., Liu, R., Feng, J., & Wang, X. (2022) · Ageing Research Reviews · doi:10.1016/j.arr.2021.101544 · Cited by 149 · see citing works
CSF biomarkers for mild cognitive impairment
Blennow, K. (2004) · Journal of Internal Medicine · doi:10.1111/j.1365-2796.2004.01368.x · Cited by 151 · see citing works
Geschwind, M. D., Haman, A., & Miller, B. L. (2007) · Neurologic Clinics · doi:10.1016/j.ncl.2007.04.001 · Cited by 143 · see citing works
Recommendations for CSF AD biomarkers in the diagnostic evaluation of dementia
Simonsen, A. H., Herukka, S.-K., Andreasen, N., Baldeiras, I., Bjerke, M., Blennow, K., Engelborghs, S., Frisoni, G. B., Gabryelewicz, T., Galluzzi, S., et al. (2017) · Alzheimer's & Dementia · doi:10.1016/j.jalz.2016.09.008 · Cited by 138 · see citing works
Martins, R. N., Villemagne, V., Sohrabi, H. R., Chatterjee, P., Shah, T. M., Verdile, G., Fraser, P., Taddei, K., Gupta, V. B., Rainey-Smith, S. R., et al. (2018) · Journal of Alzheimer’s Disease · doi:10.3233/jad-171145 · Cited by 129 · see citing works
Genetic architecture of Alzheimer's disease
Neuner, S. M., TCW, J., & Goate, A. M. (2020) · Neurobiology of Disease · doi:10.1016/j.nbd.2020.104976 · Cited by 126 · see citing works
“Research has shown that measurements of Aβ and tau in cerebrospinal fluid (CSF) exhibit high diagnostic sensitivity, with low levels of CSF Aβ42 and high levels of total tau or phosphorylated tau (particularly p-tau181) capable of differentiating AD from mild cognitive impairment and other dementias such as frontotemp…”
BackgroundCSF biomarker changes precede symptom onset of mild cognitive impairment
Moghekar, A., Li, S., Lu, Y., Li, M., Wang, M.-C., Albert, M., O’Brien, R., & For the BIOCARD Research Team (2013) · Neurology · doi:10.1212/01.wnl.0000435558.98447.17 · Cited by 103 · see citing works
Di Domenico, F., Pupo, G., Giraldo, E., Badìa, M.-C., Monllor, P., Lloret, A., Eugenia Schininà, M., Giorgi, A., Cini, C., Tramutola, A., et al. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.12.004 · Cited by 97 · 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
Kauwe, 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
Stefani, A., Sancesario, G., Pierantozzi, M., Leone, G., Galati, S., Hainsworth, A. H., & Diomedi, M. (2009) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2009.02.343 · Cited by 80 · see citing works
Preclinical validation of a potent γ-secretase modulator for Alzheimer’s disease prevention
Rynearson, K. D., Ponnusamy, M., Prikhodko, O., Xie, Y., Zhang, C., Nguyen, P., Hug, B., Sawa, M., Becker, A., Spencer, B., et al. (2021) · Journal of Experimental Medicine · doi:10.1084/jem.20202560 · Cited by 76 · see citing works
Teunissen, C. E., Veerhuis, R., De Vente, J., Verhey, F. R. J., Vreeling, F., van Boxtel, M. P. J., Glatz, J. F. C., & Pelsers, M. A. L. (2011) · European Journal of Neurology · doi:10.1111/j.1468-1331.2010.03273.x · Cited by 74 · see citing works
Ocular manifestations of Alzheimer's disease in animal models
Parnell, M., Guo, L., Abdi, M., & Cordeiro, M. F. (2012) · International Journal of Alzheimer s Disease · doi:10.1155/2012/786494 · Cited by 56 · see citing works
Haldenwanger, A., Eling, P., Kastrup, A., & Hildebrandt, H. (2010) · Journal of Alzheimer's Disease · doi:10.3233/jad-2010-101203 · Cited by 54 · see citing works
Diagnostic biomarkers in Alzheimer’s disease
Andersen, E., Casteigne, B., Chapman, W. D., Creed, A., Foster, F., Lapins, A., Shatz, R., & Sawyer, R. P. (2021) · Biomarkers in Neuropsychiatry · doi:10.1016/j.bionps.2021.100041 · Cited by 42 · see citing works
Carandini, T., Arighi, A., Sacchi, L., Fumagalli, G. G., Pietroboni, A. M., Ghezzi, L., Colombi, A., Scarioni, M., Fenoglio, C., De Riz, M. A., et al. (2019) · Alzheimer's Research & Therapy · doi:10.1186/s13195-019-0543-7 · Cited by 36 · see citing works
Blood Biomarkers for Alzheimer’s Disease: Much Promise, Cautious Progress
Keshavan, A., Heslegrave, A., Zetterberg, H., & Schott, J. M. (2017) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-016-0241-0 · Cited by 34 · see citing works
Alzheimer's disease biomarkers: correspondence between human studies and animal models
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
Constrained instruments and their application to Mendelian randomization with pleiotropy
Jiang, L., Oualkacha, K., Didelez, V., Ciampi, A., Rosa‐Neto, P., Benedet, A. L., Mathotaarachchi, S., Richards, J. B., Greenwood, C. M. T., & Initiative, A. F. T. A. D. N. (2019) · Genetic Epidemiology · doi:10.1002/gepi.22184 · Cited by 23 · see citing works
- Authors
- Sunderland, T., Linker, G., Mirza, N., Putnam, K. T., Friedman, D. L., Kimmel, L. H., Bergeson, J., Manetti, G. J., Zimmermann, M., Tang, B., Bartko, J. J., & Cohen, R. M.
- Affiliations
- National Institute of Mental Health (US)
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2003-04-23
- Volume
- 289
- Issue
- 16
- Pages
- 2094-103
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- OpenAlex
- W2295393683
- Cited by
- 656
- References
- 3
- Citations by year
- 2026: 8 · 2025: 9 · 2024: 18 · 2023: 13 · 2022: 17 · 2021: 23 · 2020: 19 · 2019: 33 · 2018: 17 · 2017: 23 · 2016: 27 · 2015: 31 · 2014: 26 · 2013: 50 · 2012: 40
- FWCI
- 18.16
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- JAMA (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Mental Health (ZO1 MH00330-14)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Cerebrospinal fluid and hydrocephalus
- Keywords
- Alzheimer's disease, cerebrospinal fluid, amyloid-beta 42, tau protein, biomarkers, diagnostic accuracy, amyloid plaques, neurofibrillary tangles, sensitivity and specificity, cognitive impairment without dementia, mild cognitive impairment
- MeSH terms
- Adult, Aged, Aged, 80 and over, Alzheimer Disease, Cross-Sectional Studies, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunoassay, Male, Middle Aged, Peptide Fragments, Biomarkers, Amyloid beta-Peptides, tau Proteins
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
