Relative Abundance of Alzheimer A Beta Amyloid Peptide Variants in Alzheimer Disease and normal Aging
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The Alzheimer A beta amyloid peptide (A beta) is the principal proteinaceous component of amyloid associated with Alzheimer disease (AD). We have determined the relative abundance of A beta structural variants present in amyloid from brains of 10 individuals with sporadic AD, 2 individuals with familial AD carrying specific mutations in the Alzheimer amyloid precursor protein gene, and 5 nondemented elderly controls. A procedure of isolation based on the extreme insolubility of A beta amyloid was used. The purified, nondigested A beta was analyzed by N-terminal sequencing and electrospray-ionization mass spectrometry. Three principal A beta variants were detected--A beta-(1-40), A beta-(1-42), and A beta-(11-42)--in all brains analyzed. The predominant variant in sporadic AD was A beta-(1-40), whereas the principal A beta variant in nondemented elderly controls was A beta-(1-42). The ratio A beta-(1-40)/A beta-(1-42) differed by 10-fold between brains from nondemented controls and those with sporadic AD.
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Schägger, H., & von Jagow, G. (1987) · Analytical Biochemistry · doi:10.1016/0003-2697(87)90587-2 · Cited by 11,420 · see citing works
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(84)80190-4 · Cited by 5,404 · see citing works
Goate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659 · see citing works
Self-citationThe precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · see citing works
Wessel, D., & Flügge, U. (1984) · Analytical Biochemistry · doi:10.1016/0003-2697(84)90782-6 · Cited by 3,997 · see citing works
The molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708 · see citing works
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499 · see citing works
Jarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178 · see citing works
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
Haass, C., Schlossmacher, M. G., Hung, A. Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B. L., Lieberburg, I., Koo, E. H., Schenk, D., Teplow, D. B., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731 · see citing works
Mullan, 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-citationCleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., & Ward, P. J. (1990) · Science · doi:10.1126/science.2111583 · Cited by 1,403 · see citing works
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014 · see citing works
Roher, A. E., Lowenson, J. D., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher-Neely, H. A., Heinrikson, R. L., & Ball, M. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53661-9 · Cited by 799 · see citing works
Roher, A. E., Lowenson, J. D., Clarke, S., Woods, A. S., Cotter, R. J., Gowing, E., & Ball, M. J. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.22.10836 · Cited by 740 · see citing works
Miller, D. L., Papayannopoulos, I. A., Styles, J., Bobin, S. A., Lin, Y. Y., Biemann, K., & Iqbal, K. (1993) · Archives of Biochemistry and Biophysics · doi:10.1006/abbi.1993.1112 · Cited by 510 · see citing works
Mass spectrometry of purified amyloid beta protein in Alzheimer's disease.
Mori, H., Takio, K., OGAWARA, M., & Selkoe, D. J. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)41896-0 · Cited by 481 · see citing works
Isolation of Low‐Molecular‐Weight Proteins from Amyloid Plaque Fibers in Alzheimer's Disease
Selkoe, D. J., Abraham, C. R., Podlisny, M. B., & Duffy, L. K. (1986) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1986.tb08501.x · Cited by 450 · see citing works
Differences Between Vascular and Plaque Core Amyloid in Alzheimer's Disease
Prelli, F., Castaño, E. M., Glenner, G. G., & Frangione, B. (1988) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1988.tb01087.x · Cited by 351 · see citing works
Protein phosphorylation inhibits production of Alzheimer amyloid beta/A4 peptide.
Buxbaum, J. D., Koo, E. H., & Greengard, P. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.19.9195 · Cited by 272 · see citing works
Self-citationRoher, A. E., WOLFE, D. E., Palutke, M., & Kukuruga, D. L. (1986) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.83.8.2662 · Cited by 136 · see citing works
Gorevic, P. D., Goñi, F., Pons‐Estel, B. A., Álvarez, F., Peress, N. S., & Frangione, B. (1986) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198611000-00004 · Cited by 124 · see citing works
Coria, F., Castaño, E. M., & Frangione, B. (1987) · PubMed Central · Cited by 120 · see citing works
β-Amyloid Protein is Higher in Alzheimerʼs Disease Brains
Frucht, S. J., & Koo, E. H. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199311000-00011 · Cited by 15 · see citing works
Characterization of Amyloid Familial β-Peptide in Familial Alzheimer′s Disease with APP717 Mutations
Liepnieks, J. J., Ghetti, B. F., Farlow, M. R., et al. (1993) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1993.2491 · Cited by 11 · see citing works
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Oxidative stress and the amyloid beta peptide in Alzheimer’s disease
Cheignon, C., Tomas, M., Bonnefont-Rousselot, D., Faller, P., Hureau, C., & Collin, F. (2018) · Redox Biology · doi:10.1016/j.redox.2017.10.014 · Cited by 2,185 · see citing works
Shibata, M., Yamada, S., Kumar, S. R., Calero, M., Bading, J., Frangione, B., Holtzman, D. M., Miller, C. A., Strickland, D. K., Ghiso, J., et al. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10498 · Cited by 1,413 · see citing works
Correlation Between Elevated Levels of Amyloid β-Peptide in the Brain and Cognitive Decline
Näslund, J. (2000) · JAMA · doi:10.1001/jama.283.12.1571 · Cited by 1,268 · see citing works
Self-citationArrest of -Amyloid Fibril Formation by a Pentapeptide Ligand
Tjernberg, L. O., Näslund, J., Lindqvist, F., Johansson, J., Karlström, A. R., Thyberg, J., Terenius, L., & Nordstedt, C. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8545 · Cited by 963 · see citing works
Self-citationReview: Alzheimer's Amyloid β-Peptide-Associated Free Radical Oxidative Stress and Neurotoxicity
Varadarajan, S., Yatin, S., Aksenova, M., & Butterfield, D. A. (2000) · Journal of Structural Biology · doi:10.1006/jsbi.2000.4274 · Cited by 735 · see citing works
Postina, R., Schroeder, A., Dewachter, I., Bohl, J., Schmitt, U., Kojro, E., Prinzen, C., Endres, K., Hiemke, C., Blessing, M., et al. (2004) · Journal of Clinical Investigation · doi:10.1172/jci20864 · Cited by 638 · see citing works
Peptide-Based Vaccines: Current Progress and Future Challenges
Malonis, R. J., Lai, J. R., & Vergnolle, O. (2020) · Chemical Reviews · doi:10.1021/acs.chemrev.9b00472 · Cited by 602 · see citing works
The redox chemistry of the Alzheimer's disease amyloid β peptide
Smith, D. G., Cappai, R., & Barnham, K. J. (2007) · Biochimica et Biophysica Acta (BBA) - Biomembranes · doi:10.1016/j.bbamem.2007.02.002 · Cited by 608 · see citing works
Wang, J., Dickson, D. W., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7085 · Cited by 567 · see citing works
Butterfield, D. A., Reed, T., Newman, S. F., & Sultana, R. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.05.037 · Cited by 564 · see citing works
Butterfield, D. A., Swomley, A. M., & Sultana, R. (2013) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5027 · Cited by 526 · see citing works
Endothelial LRP1 transports amyloid-β1–42 across the blood-brain barrier
Storck, S. E., Meister, S., Nahrath, J., Meißner, J. N., Schubert, N., Di Spiezio, A., Baches, S., Vandenbroucke, R. E., Bouter, Y., Prikulis, I., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci81108 · Cited by 477 · see citing works
Chapter 7 Protein Oxidation Processes in Aging Brain
Butterfield, D. A., & Stadtman, E. R. (1997) · Advances in cell aging and gerontology · doi:10.1016/s1566-3124(08)60057-7 · Cited by 390 · 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
Glutaminyl cyclase inhibition attenuates pyroglutamate Aβ and Alzheimer's disease–like pathology
Schilling, S., Zeitschel, U., Hoffmann, T., Heiser, U., Francke, M., Kehlen, A., Holzer, M., Hutter-Paier, B., Prokesch, M., Windisch, M., et al. (2008) · Nature Medicine · doi:10.1038/nm.1872 · Cited by 357 · see citing works
Portelius, E., Bogdanovic, N., Gustavsson, M. K., Volkmann, I., Brinkmalm, G., Zetterberg, H., Winblad, B., & Blennow, K. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0690-1 · Cited by 348 · see citing works
Self-citationAmino-terminal Deletions Enhance Aggregation of β-Amyloid Peptides in Vitro
Pike, C. J., Overman, M. J., & Cotman, C. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.23895 · Cited by 302 · see citing works
TOKUDA, T., CALERO, M., MATSUBARA, E., VIDAL, R., KUMAR, A., PERMANNE, B., ZLOKOVIC, B., SMITH, J. D., LADU, M. J., ROSTAGNO, A., et al. (2000) · Biochemical Journal · doi:10.1042/bj3480359 · Cited by 272 · see citing works
Hureau, C., & Faller, P. (2009) · Biochimie · doi:10.1016/j.biochi.2009.03.013 · Cited by 259 · see citing works
Ling, Y., Morgan, K., & Kalsheker, N. (2003) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/s1357-2725(03)00133-x · Cited by 224 · see citing works
Systemic Catabolism of Alzheimer's Aβ40 and Aβ42
Ghiso, J., Shayo, M., Calero, M., Ng, D., Tomidokoro, Y., Gandy, S., Rostagno, A., & Frangione, B. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m407668200 · Cited by 209 · see citing works
Self-citationMolecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
“APP23 transgenic mice show methionine oxidized forms of A 1-40 [64] and methionine oxidized A is also abundantly detected in AD patient brains [38, 63, 64].”
BackgroundBritschgi, M., Olin, C. E., Johns, H. T., Takeda-Uchimura, Y., LeMieux, M. C., Rufibach, K., Rajadas, J., Zhang, H., Tomooka, B., Robinson, W. H., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0904866106 · Cited by 201 · see citing works
Kuo, Y.-M., Emmerling, M. R., Woods, A. S., Cotter, R. J., & Roher, A. E. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.7083 · Cited by 178 · see citing works
Bouter, Y., Dietrich, K., Wittnam, J. L., Rezaei-Ghaleh, N., Pillot, T., Papot-Couturier, S., Lefebvre, T., Sprenger, F., Wirths, O., Zweckstetter, M., et al. (2013) · Acta Neuropathologica · doi:10.1007/s00401-013-1129-2 · Cited by 175 · see citing works
Roberts, B. R., Lind, M., Wagen, A. Z., Rembach, A., Frugier, T., Li, Q.-X., Ryan, T. M., McLean, C. A., Doecke, J. D., Rowe, C. C., et al. (2017) · Brain · doi:10.1093/brain/awx057 · Cited by 143 · see citing works
Methionine-35 of A <i>β</i> (1–42): Importance for Oxidative Stress in Alzheimer Disease
Butterfield, D. A., & Sultana, R. (2011) · Journal of Amino Acids · doi:10.4061/2011/198430 · Cited by 124 · see citing works
Lacosta, A.-M., Pascual-Lucas, M., Pesini, P., Casabona, D., Pérez-Grijalba, V., Marcos-Campos, I., Sarasa, L., Canudas, J., Badi, H., Monleón, I., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0340-8 · Cited by 111 · see citing works
Yang, A. J., Chandswangbhuvana, D., Shu, T., Henschen, A., & Glabe, C. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20650 · Cited by 108 · see citing works
Delineating the Mechanism of Alzheimer’s Disease Aβ Peptide Neurotoxicity
Cappai, R., & Barnham, K. J. (2008) · Neurochemical Research · doi:10.1007/s11064-007-9469-8 · Cited by 108 · see citing works
Clementi, M. E., Pezzotti, M., Orsini, F., Sampaolese, B., Mezzogori, D., Grassi, C., Giardina, B., & Misiti, F. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.01.137 · Cited by 105 · see citing works
Cheignon, C., Faller, P., Testemale, D., Hureau, C., & Collin, F. (2016) · Metallomics · doi:10.1039/c6mt00150e · Cited by 81 · see citing works
Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73 · see citing works
Antonios, G., Saiepour, N., Bouter, Y., Richard, B. C., Paetau, A., Verkkoniemi-Ahola, A., Lannfelt, L., Ingelsson, M., Kovacs, G. G., Pillot, T., et al. (2013) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-1-56 · Cited by 53 · see citing works
Self-citationAkram, A., Schmeidler, J., Katsel, P., Hof, P. R., & Haroutunian, V. (2010) · Brain Research · doi:10.1016/j.brainres.2010.01.006 · Cited by 50 · see citing works
Meißner, J. N., Bouter, Y., & Bayer, T. A. (2015) · Journal of Alzheimer s Disease · doi:10.3233/jad-142868 · Cited by 16 · see citing works
A Chronological Review of Potential Disease-Modifying Therapeutic Strategies for Alzheimer’s Disease
Ettcheto, M., Busquets, O., Espinosa-Jiménez, T., Verdaguer, E., Auladell, C., & Camins, A. (2020) · Current Pharmaceutical Design · doi:10.2174/1381612826666200211121416 · Cited by 13 · see citing works
Beta-amyloid oligomers: recent developments
Borutaite, V., Morkuniene, R., & Valincius, G. (2011) · bmc · doi:10.1515/bmc.2011.019 · Cited by 9 · see citing works
- Authors
- Näslund, J., Schierhorn, A., Hellman, U., Lannfelt, L., Roses, A. D., Tjernberg, L. O., Silberring, J., Gandy, S. E., Winblad, B., & Greengard, P.
- Affiliations
- Karolinska Institutet (SE)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1994-08-30
- Volume
- 91
- Issue
- 18
- Pages
- 8378-8382
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC44609
- OpenAlex
- W1989972829
- Cited by
- 468
- References
- 27
- Citations by year
- 2026: 4 · 2025: 13 · 2024: 13 · 2023: 31 · 2022: 19 · 2021: 16 · 2020: 13 · 2019: 20 · 2018: 17 · 2017: 25 · 2016: 12 · 2015: 18 · 2014: 9 · 2013: 10 · 2012: 20
- FWCI
- 7.01
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01hl049571-03)
- Medical Research Council
- National Institute on Aging (P01AG010491, AG09464, AG10491, P01AG009464)
- National Heart, Lung, and Blood Institute (HL 49571-02)
- 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
- Alzheimer's disease, amyloid-beta, sporadic Alzheimer's disease, familial Alzheimer's disease, APP mutations, normal aging, amyloid precursor protein, peptide isoforms
- MeSH terms
- Aged, Aging, Alzheimer Disease, Amino Acid Sequence, Cerebral Cortex, Female, Humans, Male, Molecular Sequence Data, Mutation, Mass Spectrometry, Amyloid beta-Peptides, Amyloid beta-Protein Precursor
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