Amyloid‐β oligomers are inefficiently measured by enzyme‐linked immunosorbent assay
Abstract
Amyloid‐β (Aβ) peptide levels are widely measured by enzyme‐linked immunosorbent assay (ELISA) in Alzheimer's disease research. Here, we show that oligomerization of Aβ results in underestimated Aβ ELISA levels. The implications are that comprehensive analysis of soluble Aβ requires either sample pretreatment at denaturing conditions or novel conformation‐dependent immunoassays. Our findings might be of relevance for many neurodegenerative disorders in which soluble protein aggregates are the main neurotoxic species. Ann Neurol 2005;58:147–150
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In a study using ELISA, when the same amounts of Aβ1-42 were incubated over time, levels of Aβ42 assayed by a standard non-denaturing ELISA appeared to decline as a function of time, while denaturing Western blotting indicated that levels were actually unchanged; this occurred because ongoing Aβ aggregation progressively blocked access of the Aβ42 antibody in the ELISA.
“When the same amounts of Aβ1-42 were incubated over time, levels of Aβ42 assayed by a standard non-denaturing ELISA appeared to decline as a function of time, while denaturing Western blotting indicated that levels were actually unchanged; this occurred because ongoing Aβ aggregation progressively blocked access of the Aβ42 antibody in the ELISA.”
From Intraneuronal β-amyloid accumulation and synapse pathology in Alzheimer’s disease (2010) · cites this paper as [181]
Cites
Common structure of soluble amyloid oligomers implies common mechanism of pathogenesis
Kayed, R., Head, E., Thompson, J. L., McIntire, T. M., Milton, S. C., Cotman, C. W., & Glabe, C. G. (2003) · Science · doi:10.1126/science.1079469 · Cited by 4,064 · see citing works
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Self-citationMullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., & Lannfelt, L. (1992) · Nature Genetics · doi:10.1038/ng0892-345 · Cited by 1,513 · see citing works
Self-citationThe 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation
Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., et al. (2001) · Nature Neuroscience · doi:10.1038/nn0901-887 · Cited by 1,209 · see citing works
Self-citationAmyloid β-Protein Fibrillogenesis
Walsh, D. M., Lomakin, A., Benedek, G. B., Condron, M. M., & Teplow, D. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.35.22364 · Cited by 1,139 · see citing works
Gong, Y., Chang, L., Viola, K. L., Lacor, P. N., Lambert, M. P., Finch, C. E., Krafft, G. A., & Klein, W. L. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1834302100 · Cited by 1,061 · see citing works
Amyloid β-Protein Fibrillogenesis
Walsh, D. M., Hartley, D. M., Kusumoto, Y., Fezoui, Y., Condron, M. M., Lomakin, A., Benedek, G. B., Selkoe, D. J., & Teplow, D. B. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.36.25945 · Cited by 1,046 · see citing works
Motter, 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
Observation of metastable Aβ amyloid protofibrils by atomic force microscopy
Harper, J. D., Wong, S. S., Lieber, C. M., & Lansbury, P. T. (1997) · Chemistry & Biology · doi:10.1016/s1074-5521(97)90255-6 · Cited by 691 · see citing works
Hoshi, M. M., Sato, M., Matsumoto, S., Noguchi, A., Yasutake, K., Yoshida, N., & Sato, K. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1237107100 · Cited by 494 · see citing works
Lord, A., Kalimo, H., Eckman, C., Zhang, X.-Q., Lannfelt, L., & Nilsson, L. N. G. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.12.007 · Cited by 260 · see citing works
Self-citationHigh Levels of Circulating Aβ42 Are Sequestered by Plasma Proteins in Alzheimer's Disease
Kuo, Y., Emmerling, M. R., Lampert, H. C., Hempelman, S. R., Kokjohn, T. A., Woods, A. S., Cotter, R. J., & Roher, A. E. (1999) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1999.0552 · Cited by 182 · see citing works
Aggressive amyloidosis in mice expressing human amyloid peptides with the Arctic mutation
Cheng, I. H.-J., Palop, J. J., Esposito, L., Bien‐Ly, N., Yan, F., & Mucke, L. (2004) · Nature Medicine · doi:10.1038/nm1123 · Cited by 132 · see citing works
Oligomerization and fibril assembly of the amyloid-β protein
Roher, A. E., Baudry, J. Y., Chaney, M. O., Kuo, Y., Stine, W. B., & Emmerling, M. R. (2000) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/s0925-4439(00)00030-2 · Cited by 87 · see citing works
The Arctic mutation interferes with processing of the amyloid precursor protein
Stenh, C., Nilsberth, C., ck, J. H., Engvall, B., Nšslund, J., & Lannfelt, L. (2002) · Neuroreport · doi:10.1097/00001756-200210280-00005 · Cited by 52 · see citing works
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Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · see citing works
Intraneuronal 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
Self-citationSensitive ELISA detection of amyloid‐β protofibrils in biological samples
Englund, H., Sehlin, D., Johansson, A., Nilsson, L. N. G., Gellerfors, P., Paulie, S., Lannfelt, L., & Pettersson, F. E. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.04759.x · Cited by 292 · see citing works
Self-citationBasun, H., Bogdanovic, N., Ingelsson, M., Almkvist, O., Näslund, J., Axelman, K., Bird, T. D., Nochlin, D., Schellenberg, G. D., Wahlund, L.-O., et al. (2008) · Archives of Neurology · doi:10.1001/archneur.65.4.499 · Cited by 115 · see citing works
Self-citationDistinct Pools of β-Amyloid in Alzheimer Disease–Affected Brain: A Clinicopathologic Study
Steinerman, J. R., Irizarry, M., Scarmeas, N., Raju, S., Brandt, J., Albert, M., Blacker, D., Hyman, B., & Stern, Y. (2008) · Archives of Neurology · doi:10.1001/archneur.65.7.906 · Cited by 104 · see citing works
- Authors
- Stenh, C., Englund, H., Lord, A., Johansson, A., Almeida, C. G., Gellerfors, P., Greengard, P., Gouras, G. K., Lannfelt, L., & Nilsson, L. N. G.
- Affiliations
- Uppsala University (SE)
- Rockefeller University (US)
- Cornell University (US)
- Corresponding author
- Lannfelt, Lars
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2005-06-27
- Volume
- 58
- Issue
- 1
- Pages
- 147-150
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- OpenAlex
- W2058432632
- Cited by
- 99
- References
- 17
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 1 · 2018: 6 · 2017: 1 · 2016: 4 · 2015: 8 · 2014: 4 · 2013: 5 · 2012: 5
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Neurology (publishedVersion)
- PubMed (publishedVersion)
- Lund University Publications (Lund University) (submittedVersion)
- Funders
- National Institute on Aging (AG09464, P01AG009464)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- amyloid-beta oligomers, amyloid-beta, enzyme-linked immunosorbent assay, oligomerization, Alzheimer's disease, sample preparation, neurodegenerative diseases
- MeSH terms
- Alzheimer Disease, Animals, Cell Line, Enzyme-Linked Immunosorbent Assay, Humans, Mice, Transgenic, Mutation, Transfection, Blotting, Western, Amyloid beta-Peptides, Mice
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