Rapid induction of Alzheimer A beta amyloid formation by zinc

Bush, A.; Pettingell, W.; Multhaup, G; d Paradis, M; Vonsattel, J.; Gusella, J.; Beyreuther, K; Masters, C.; Tanzi, R.

doi:10.1126/science.8073293

Cited by 1,522Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchTrace Elements in Health

Rapid induction of Alzheimer A beta amyloid formation by zinc

Bush, A., Pettingell, W., Multhaup, G, d Paradis, M, Vonsattel, J., Gusella, J., Beyreuther, K, Masters, C. +1 more·1994·Science

DOI 10.1126/science.8073293

Open this paper in CoChat — free account

Abstract

A beta 1-40, a major component of Alzheimer's disease cerebral amyloid, is present in the cerebrospinal fluid and remains relatively soluble at high concentrations (less than or equal to 3.7 mM). Thus, physiological factors which induce A beta amyloid formation could provide clues to the pathogenesis of the disease. It has been shown that human A beta specifically and saturably binds zinc. Here, concentrations of zinc above 300 nM rapidly destabilized human A beta 1-40 solutions, inducing tinctorial amyloid formation. However, rat A beta 1-40 binds zinc less avidly and is immune to these effects, perhaps explaining the scarcity with which these animals form cerebral A beta amyloid. These data suggest a role for cerebral zinc metabolism in the neuropathogenesis of Alzheimer's disease.

Integrity signals

Registry

Crossref · 10.1126/science.8073293

Cites

31 of 31 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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?

Metal ions promote Aβ aggregation and formation of reactive oxygen species and lead to oxidative stress.
“For example, it was shown that that metal ions promote Aβ aggregation,16,17 as well as formation of reactive oxygen species (ROS) and lead to oxidative stress.18–20”
From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [16]
Zn2+ promotes formation of nonfibrillar aggregates.
“Several studies showed that Zn2+ promotes formation of nonfibrillar aggregates,16,29–31 yet conflicting results have been reported for the Cu2+-mediated Aβ aggregation.”
From The effect of Cu2+ and Zn2+ on the Aβ42 peptide aggregation and cellular toxicity (2013) · cites this paper as [16]
Copper, iron, and zinc ions affect Aβ aggregation and lead to formation of reactive oxygen species.
“These metal ions have been shown to affect Aβ aggregation, as well as lead to the formation of reactive oxygen species (ROS).12−16”
From Small Bifunctional Chelators That Do Not Disaggregate Amyloid β Fibrils Exhibit Reduced Cellular Toxicity (2014) · cites this paper as [12]

Alzheimer's disease: Initial report of the purification and characterization of a novel cerebrovascular amyloid protein
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
Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease
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
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
Self-citation
The carboxy terminus of the .beta. amyloid protein is critical for the seeding of amyloid formation: Implications for the pathogenesis of Alzheimer's disease
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022 · see citing works
Amyloid Deposits and Amyloidosis
Glenner, G. G. (1980) · New England Journal of Medicine · doi:10.1056/nejm198006053022305 · Cited by 1,794 · 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
A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N–terminus of β–amyloid
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
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
Shoji, M., Golde, T. E., Ghiso, J., Cheung, T. T., Estus, S., Shaffer, L. M., Cai, X.-D., McKay, D. M., Tintner, R., Frangione, B., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447 · see citing works
Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type
Levy, E., Carman, M. D., Fernandez-Madrid, I. J., Power, M. D., Lieberburg, I. M., van Duinen, S. G., Bots, G. T. A. M., Luyendijk, W., & Frangione, B. (1990) · Science · doi:10.1126/science.2111584 · Cited by 1,380 · see citing works
Early-onset Alzheimer's disease caused by mutations at codon 717 of the β-amyloid precursor protein gene
Chartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., et al. (1991) · Nature · doi:10.1038/353844a0 · Cited by 1,214 · see citing works
Release of endogenous Zn2+ from brain tissue during activity
Assaf, S. Y., & Chung, S. (1984) · Nature · doi:10.1038/308734a0 · Cited by 1,129 · see citing works
A mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's Disease
Murrell, J. R., Farlow, M. R., Ghetti, B. F., & Benson, M. D. (1991) · Science · doi:10.1126/science.1925564 · Cited by 1,122 · see citing works
Stimulation-induced uptake and release of zinc in hippocampal slices
Howell, G. A., Welch, M. G., & Frederickson, C. (1984) · Nature · doi:10.1038/308736a0 · Cited by 820 · see citing works
Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the β–amyloid precursor protein gene
Hendriks, L., van Duijn, C. M., Cras, P. P., Cruts, M., Hul, W. V., van Harskamp, F., Warren, A., McInnis, M. G., Antonarakis, S. E., Martin, J., et al. (1992) · Nature Genetics · doi:10.1038/ng0692-218 · Cited by 735 · see citing works
The growth inhibitory factor that is deficient in the Alzheimer's disease brain is a 68 amino acid metallothionein-like protein
Uchida, Y., Takio, K., Titani, K., Ihara, Y., & Tomonaga, M. (1991) · Neuron · doi:10.1016/0896-6273(91)90272-2 · Cited by 700 · see citing works
Perforant pathway changes and the memory impairment of Alzheimer's disease
Hyman, B. T., Van Hoesen, G. W., Kromer, L. J., & Damasio, A. R. (1986) · Annals of Neurology · doi:10.1002/ana.410200406 · Cited by 672 · see citing works
Amyloid A4 Protein and Its Precursor in Down's Syndrome and Alzheimer's Disease
Rumble, B. A., Retallack, R. W., Hilbich, C., Simms, G., Multhaup, G., Martins, R. N., Hockey, A., Montgomery, P., Beyreuther, K. T., & Masters, C. L. (1989) · New England Journal of Medicine · doi:10.1056/nejm198906013202203 · Cited by 652 · see citing works
Self-citation
Aggregation and secondary structure of synthetic amyloid βA4 peptides of Alzheimer's disease
Hilbich, C., Kisters–Woike, B., Reed, J., Masters, C. L., & Beyreuther, K. T. (1991) · Journal of Molecular Biology · doi:10.1016/0022-2836(91)90881-6 · Cited by 580 · see citing works
Self-citation
Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells.
Busciglio, J., Gabuzda, D. H., Matsudaira, P., & Yankner, B. A. (1993) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.90.5.2092 · Cited by 569 · see citing works
Journal of Mental Deficiency Research
Richards, B. W. (1980) · Journal of Intellectual & Developmental Disability · doi:10.3109/13668258009016114 · Cited by 506 · see citing works
Aluminum, Iron, and Zinc Ions Promote Aggregation of Physiological Concentrations of β‐Amyloid Peptide
Mantyh, P. W., Ghilardi, J. R., Rogers, S. D., DeMaster, E., Allen, C. J., Stimson, E. R., & Maggio, J. E. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03639.x · Cited by 464 · see citing works
Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat
Frederickson, C. J., Klitenick, M. A., Manton, W. I., & Kirkpatrick, J. B. (1983) · Brain Research · doi:10.1016/0006-8993(83)90858-2 · Cited by 346 · see citing works
Modulation of A beta adhesiveness and secretase site cleavage by zinc.
Bush, A. I., Pettingell, W. H., Paradis, M. D., & Tanzi, R. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32694-7 · Cited by 331 · see citing works
Self-citation
Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis
Johnstone, E. M., Chaney, M. O., Norris, F. H., Pascual, R. V., & Little, S. H. (1991) · Molecular Brain Research · doi:10.1016/0169-328x(91)90088-f · Cited by 312 · see citing works
Trace element imbalances in isolated subcellular fractions of Alzheimer's disease brains
Wenstrup, D. E., Ehman, W. D., & Markesbery, W. R. (1990) · Brain Research · doi:10.1016/0006-8993(90)91804-p · Cited by 189 · see citing works
Kinetics of aggregation of synthetic β-amyloid peptide
Tomski, S. J., & Murphy, R. M. (1992) · Archives of Biochemistry and Biophysics · doi:10.1016/0003-9861(92)90735-f · Cited by 149 · see citing works
Cerebrospinal fluid trace element content in dementia
Hershey, C. O., Hershey, L. A., Varnes, A. W., Vibhakar, S. D., Lavin, P., & Strain, W. H. (1983) · Neurology · doi:10.1212/wnl.33.10.1350 · Cited by 121 · see citing works
Characterization of Neutral Proteinases from Alzheimer‐Affected and Control Brain Specimens: Identification of Calcium‐Dependent Metalloproteinases from the Hippocampus
Backstrom, J. R., Miller, C. A., & Tökés, Z. A. (1992) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1992.tb09352.x · Cited by 109 · see citing works
The Structure of Neuritic Plaques in the Cerebral Cortex of Aged Rats
Vaughan, D. W., & Peters, A. (1981) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-198107000-00009 · Cited by 78 · see citing works
Cholinergic denervation-induced increase of chelatable zinc in mossy-fiber region of the hippocampal formation
Stewart, G. R., Frederickson, C. J., Howell, G. A., & Gage, F. H. (1984) · Brain Research · doi:10.1016/0006-8993(84)90734-0 · Cited by 70 · see citing works
[Alzheimer's disease and the zinc theory].
Constantinidis, J. (1990) · PubMed · Cited by 31 · see citing works

Flagged first, then by citations

Sorted by citations

The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Oxidative stress, aging, and diseases
Liguori, I., Russo, G., Curcio, F., Bulli, G., Aran, L., Della-Morte, D., Gargiulo, G., Testa, G., Cacciatore, F., Bonaduce, D., et al. (2018) · Clinical Interventions in Aging · doi:10.2147/cia.s158513 · Cited by 3,979 · see citing works
Copper, iron and zinc in Alzheimer's disease senile plaques
Lovell, M. A., Robertson, J. D., Teesdale, W. J., Campbell, J. L., & Markesbery, W. R. (1998) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(98)00092-6 · Cited by 2,120 · see citing works
Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging
Que, E. L., Domaille, D. W., & Chang, C. J. (2008) · Chemical Reviews · doi:10.1021/cr078203u · Cited by 2,063 · see citing works
The neurobiology of zinc in health and disease
Frederickson, C. J., Koh, J., & Bush, A. I. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1671 · Cited by 1,841 · see citing works
Self-citation
Oxidative Stress, Synaptic Dysfunction, and Alzheimer’s Disease
Tönnies, E., & Trushina, E. (2017) · Journal of Alzheimer s Disease · doi:10.3233/jad-161088 · Cited by 1,750 · see citing works
Copper Homeostasis and Neurodegenerative Disorders (Alzheimer's, Prion, and Parkinson's Diseases and Amyotrophic Lateral Sclerosis)
Gaggelli, E., Kozlowski, H., Valensin, D., & Valensin, G. (2006) · Chemical Reviews · doi:10.1021/cr040410w · Cited by 1,729 · see citing works
MODELS OF AMYLOID SEEDING IN ALZHEIMER'S DISEASE AND SCRAPIE: Mechanistic Truths and Physiological Consequences of the Time-Dependent Solubility of Amyloid Proteins
Harper, J. D., & Lansbury, P. T. (1997) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.66.1.385 · Cited by 1,652 · see citing works
Treatment with a Copper-Zinc Chelator Markedly and Rapidly Inhibits β-Amyloid Accumulation in Alzheimer's Disease Transgenic Mice
Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y.-S., et al. (2001) · Neuron · doi:10.1016/s0896-6273(01)00317-8 · Cited by 1,447 · see citing works
Self-citation
Iron accumulation in Alzheimer disease is a source of redox-generated free radicals
Smith, M. A., Harris, P. L. R., Sayre, L. M., & Perry, G. L. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.18.9866 · Cited by 1,357 · see citing works
The metallobiology of Alzheimer's disease
Bush, A. I. (2003) · Trends in Neurosciences · doi:10.1016/s0166-2236(03)00067-5 · Cited by 1,315 · see citing works
Self-citation
Trace elements in human physiology and pathology: zinc and metallothioneins
Tapiero, H., & Tew, K. D. (2003) · Biomedicine & Pharmacotherapy · doi:10.1016/s0753-3322(03)00081-7 · Cited by 1,297 · see citing works
Oxidative stress and Alzheimer disease
Christen, Y. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.2.621s · Cited by 1,158 · see citing works
Recent advances in Alzheimer's disease: Mechanisms, clinical trials and new drug development strategies.
Zhang, J., Zhang, Y., Wang, J., Xia, Y., Zhang, J., & Chen, L. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01911-3 · Cited by 1,138 · see citing works
The Aβ Peptide of Alzheimer's Disease Directly Produces Hydrogen Peroxide through Metal Ion Reduction
Huang, X., Atwood, C., Hartshorn, M. A., Multhaup, G., Goldstein, L. E., Scarpa, R. C., Cuajungco, M. P., Gray, D. N., Lim, J. T., Moir, R. D., et al. (1999) · Biochemistry · doi:10.1021/bi990438f · Cited by 1,107 · see citing works
Self-citation
Dramatic Aggregation of Alzheimer Aβ by Cu(II) Is Induced by Conditions Representing Physiological Acidosis
Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009 · see citing works
Self-citation
Fluorescent chemosensors for Zn2+
Xu, Z., Yoon, J., & Spring, D. R. (2010) · Chemical Society Reviews · doi:10.1039/b916287a · Cited by 983 · see citing works
Age-related macular degeneration: etiology, pathogenesis, and therapeutic strategies
Ambati, J., Ambati, B. K., Yoo, S. H., Ianchulev, S., & Adamis, A. P. (2003) · Survey of Ophthalmology · doi:10.1016/s0039-6257(03)00030-4 · Cited by 959 · see citing works
Mechanisms of Neuronal Degeneration in Alzheimer's Disease
Yankner, B. A. (1996) · Neuron · doi:10.1016/s0896-6273(00)80115-4 · Cited by 947 · see citing works
Self-assembling peptide and protein amyloids: from structure to tailored function in nanotechnology
Wei, G., Su, Z., Reynolds, N. P., Arosio, P., Hamley, I. W., Gazit, E., & Mezzenga, R. (2017) · Chemical Society Reviews · doi:10.1039/c6cs00542j · Cited by 903 · see citing works
The Amyloid Beta Peptide: A Chemist’s Perspective. Role in Alzheimer’s and Fibrillization
Hamley, I. W. (2012) · Chemical Reviews · doi:10.1021/cr3000994 · Cited by 881 · see citing works
Oxidative Stress and the Pathogenesis of Alzheimer's Disease
Zhao, Y., & Zhao, B. (2013) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2013/316523 · Cited by 855 · see citing works
Inclusion body myositis and myopathies
Griggs, R. C., Askanas, V., DiMauro, S., Engel, A., Karpati, G., Mendell, J. R., & Rowland, L. P. (1995) · Annals of Neurology · doi:10.1002/ana.410380504 · Cited by 834 · see citing works
Zinc in the physiology and pathology of the CNS
Sensi, S. L., Paoletti, P., Bush, A. I., & Sekler, I. (2009) · Nature Reviews Neuroscience · doi:10.1038/nrn2734 · Cited by 759 · see citing works
Self-citation
ZINC AND BRAIN INJURY
Choi, D. W., & Koh, J. Y. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.347 · Cited by 754 · see citing works
Molecular pathways to neurodegeneration
Bossy-Wetzel, E., Schwarzenbacher, R., & Lipton, S. A. (2004) · Nature Medicine · doi:10.1038/nm1067 · Cited by 740 · see citing works
Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease: a phase IIa, double-blind, randomised, placebo-controlled trial
Lannfelt, L., Blennow, K., Zetterberg, H., Batsman, S., Ames, D., Harrison, J., Masters, C. L., Targum, S., Bush, A. I., Murdoch, R., et al. (2008) · The Lancet Neurology · doi:10.1016/s1474-4422(08)70167-4 · Cited by 725 · see citing works
Self-citation
History and progress of hypotheses and clinical trials for Alzheimer’s disease
Liu, P.-P., Xie, Y., Meng, X.-Y., & Kang, J.-S. (2019) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-019-0063-8 · Cited by 723 · see citing works
Overcoming the Blood–Brain Barrier: The Role of Nanomaterials in Treating Neurological Diseases
Furtado, D., Björnmalm, M., Ayton, S., Bush, A. I., Kempe, K., & Caruso, F. (2018) · Advanced Materials · doi:10.1002/adma.201801362 · Cited by 708 · see citing works
Self-citation
Zn2+-Triggered Amide Tautomerization Produces a Highly Zn2+-Selective, Cell-Permeable, and Ratiometric Fluorescent Sensor
Xu, Z., Baek, K.-H., Kim, H., Cui, J., Qian, X. H., Spring, D. R., Shin, I., & Yoon, J. (2009) · Journal of the American Chemical Society · doi:10.1021/ja907334j · Cited by 692 · see citing works
Identification and characterization of key kinetic intermediates in amyloid β-protein fibrillogenesis11Edited by F. Cohen
Kirkitadze, M. D., Condron, M. M., & Teplow, D. B. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4970 · Cited by 684 · see citing works
Iron-Export Ferroxidase Activity of β-Amyloid Precursor Protein Is Inhibited by Zinc in Alzheimer's Disease
Duce, J. A., Tsatsanis, A., Cater, M. A., James, S., Robb, E. L., Wikhe, K., Leong, S. L., Perez, K. A., Johanssen, T., Greenough, M. A., et al. (2010) · Cell · doi:10.1016/j.cell.2010.08.014 · Cited by 682 · see citing works
Self-citation
Bioinorganic Chemistry of Alzheimer’s Disease
Kepp, K. P. (2012) · Chemical Reviews · doi:10.1021/cr300009x · Cited by 672 · see citing works
Rapid Restoration of Cognition in Alzheimer's Transgenic Mice with 8-Hydroxy Quinoline Analogs Is Associated with Decreased Interstitial Aβ
Adlard, P. A., Cherny, R. A., Finkelstein, D. I., Gautier, E., Robb, E., Cortes, M., Volitakis, I., Liu, X., Smith, J. P., Perez, K., et al. (2008) · Neuron · doi:10.1016/j.neuron.2008.06.018 · Cited by 672 · see citing works
Self-citation
Alzheimer's Disease Amyloid-β Binds Copper and Zinc to Generate an Allosterically Ordered Membrane-penetrating Structure Containing Superoxide Dismutase-like Subunits
Curtain, C. C., Ali, F. E. A., Volitakis, I., Cherny, R. A., Norton, R. S., Beyreuther, K. T., Barrow, C. J., Masters, C. L., Bush, A. I., & Barnham, K. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100175200 · Cited by 653 · see citing works
Self-citation
Amyloid β protein forms ion channels: implications for Alzheimer's disease pathophysiology
LIN, H., Bhatia, R., & Lal, R. (2001) · The FASEB Journal · doi:10.1096/fj.01-0377com · Cited by 641 · see citing works
Characterization of Copper Interactions with Alzheimer Amyloid β Peptides: Identification of an Attomolar‐Affinity Copper Binding Site on Amyloid β1‐42
Atwood, C. S., Scarpa, R. C., Huang, X., Moir, R. D., Jones, W. D., Fairlie, D. P., Tanzi, R. E., & Bush, A. I. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751219.x · Cited by 641 · see citing works
Self-citation
Water-soluble Aβ(N-40, N-42) oligomers in normal and Alzheimer disease brains
Kuo, Y.-M., Emmerling, M. R., Vigo-Pelfrey, C., Kasunic, T. C., Kirkpatrick, J. B., Murdoch, G. H., Ball, M. J., & Roher, A. E. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4077 · Cited by 618 · see citing works
Development of Multifunctional Molecules as Potential Therapeutic Candidates for Alzheimer’s Disease, Parkinson’s Disease, and Amyotrophic Lateral Sclerosis in the Last Decade
Savelieff, M. G., Nam, G., Kang, J., Lee, H. J., Lee, M., & Lim, M. H. (2018) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00138 · Cited by 603 · see citing works
Induction of nitric oxide-dependent apoptosis in motor neurons by zinc-deficient superoxide dismutase
Estévez, A. G., Crow, J. P., Sampson, J. B., Reiter, C., Zhuang, Y., Richardson, G. J., Tarpey, M. M., Barbeito, L., & Beckman, J. S. (1999) · Science · doi:10.1126/science.286.5449.2498 · Cited by 596 · see citing works
Synchrotron-based infrared and X-ray imaging shows focalized accumulation of Cu and Zn co-localized with β-amyloid deposits in Alzheimer’s disease
Miller, L. M., Wang, Q., Telivala, T. P., Smith, R., Lanzirotti, A., & Judith Miklossy, A. (2005) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.09.004 · Cited by 588 · see citing works
Metalloenzyme-like Activity of Alzheimer's Disease β-Amyloid
Opazo, C., Huang, X., Cherny, R. A., Moir, R. D., Roher, A. E., White, A. R., Cappai, R., Masters, C. L., Tanzi, R. E., Inestrosa, N. C., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m206428200 · Cited by 580 · see citing works
Self-citation
Zn2+: a novel ionic mediator of neural injury in brain disease
Weiss, J. H., Sensi, S. L., & Koh, J. Y. (2000) · Trends in Pharmacological Sciences · doi:10.1016/s0165-6147(00)01541-8 · Cited by 575 · see citing works
Therapeutics for Alzheimer's Disease Based on the Metal Hypothesis
Bush, A. I., & Tanzi, R. E. (2008) · Neurotherapeutics · doi:10.1016/j.nurt.2008.05.001 · Cited by 566 · see citing works
Self-citation
An iron-responsive element type II in the 5'-untranslated region of the Alzheimer's amyloid precursor protein transcript
Rogers, J. T., Randall, J. D., Cahill, C. M., Eder, P. S., Huang, X., Gunshin, H., Leiter, L., McPhee, J., Sarang, S. S., Utsuki, T., et al. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207435200 · Cited by 551 · see citing works
Self-citation
Zinc Metabolism in the Brain: Relevance to Human Neurodegenerative Disorders
Cuajungco, M. P., & Lees, G. J. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0163 · Cited by 540 · see citing works
Copper, iron, and zinc imbalances in severely degenerated brain regions in Alzheimer’s disease: possible relation to oxidative stress.
Deibel, M. A., Ehmann, W. D., & Markesbery, W. R. (1996) · Journal of the Neurological Sciences · doi:10.1016/s0022-510x(96)00203-1 · Cited by 540 · see citing works
Bioinorganic chemistry of copper and zinc ions coordinated to amyloid-β peptide
Faller, P., & Hureau, C. (2009) · Dalton Trans. · doi:10.1039/b813398k · Cited by 530 · see citing works
Prion Protein Selectively Binds Copper(II) Ions
Stöckel, J., Safar, J., Wallace, A. C., Cohen, F. E., & Prusiner, S. B. (1998) · Biochemistry · doi:10.1021/bi972827k · Cited by 518 · see citing works
Critical Review of Exposure and Effects: Implications for Setting Regulatory Health Criteria for Ingested Copper
Taylor, A. A., Tsuji, J. S., Garry, M. R., McArdle, M. E., Goodfellow, W. L., Adams, W. J., & Menzie, C. A. (2019) · Environmental Management · doi:10.1007/s00267-019-01234-y · Cited by 518 · see citing works
Copper in disorders with neurological symptoms: Alzheimer’s, Menkes, and Wilson diseases
Strausak, D., Mercer, J. F. B., Dieter, H. H., Stremmel, W., & Multhaup, G. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00454-3 · Cited by 508 · see citing works
Self-citation
Biological metals and metal-targeting compounds in major neurodegenerative diseases
Barnham, K. J., & Bush, A. I. (2014) · Chem. Soc. Rev. · doi:10.1039/c4cs00138a · Cited by 497 · see citing works
Self-citation
Aqueous Dissolution of Alzheimer's Disease Aβ Amyloid Deposits by Biometal Depletion
Cherny, R. A., Legg, J. T., McLean, C. A., Fairlie, D. P., Huang, X., Atwood, C. S., Beyreuther, K., Tanzi, R. E., Masters, C. L., & Bush, A. I. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.33.23223 · Cited by 482 · see citing works
Self-citation
Myelin dysfunction drives amyloid-β deposition in models of Alzheimer’s disease
Depp, C., Sun, T., Sasmita, A. O., Spieth, L., Berghoff, S. A., Nazarenko, T., Overhoff, K., Steixner-Kumar, A. A., Subramanian, S., Arinrad, S., et al. (2023) · Nature · doi:10.1038/s41586-023-06120-6 · Cited by 476 · see citing works
Metal Toxicity Links to Alzheimer's Disease and Neuroinflammation
Huat, T. J., Camats‐Perna, J., Newcombe, E. A., Valmas, N., Kitazawa, M., & Medeiros, R. (2019) · Journal of Molecular Biology · doi:10.1016/j.jmb.2019.01.018 · Cited by 483 · see citing works
Amyloid Precursor Protein, Presenilins, and α-Synuclein: Molecular Pathogenesis and Pharmacological Applications in Alzheimer’s Disease
Suh, Y.-H., & Checler, F. (2002) · Pharmacological Reviews · doi:10.1124/pr.54.3.469 · Cited by 467 · see citing works
Copper Binding to the Amyloid-β (Aβ) Peptide Associated with Alzheimer's Disease
Syme, C. D., Nadal, R. C., Rigby, S. E. J., & Viles, J. H. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m313572200 · Cited by 459 · see citing works
The Role of Environmental Exposures in Neurodegeneration and Neurodegenerative Diseases
Cannon, J. R., & Greenamyre, J. T. (2011) · Toxicological Sciences · doi:10.1093/toxsci/kfr239 · Cited by 462 · see citing works
Metal dyshomeostasis and oxidative stress in Alzheimer’s disease
Greenough, M. A., Camakaris, J., & Bush, A. I. (2012) · Neurochemistry International · doi:10.1016/j.neuint.2012.08.014 · Cited by 439 · see citing works
Self-citation
Contribution by synaptic zinc to the gender-disparate plaque formation in human Swedish mutant APP transgenic mice
Lee, J., Cole, T. B., Palmiter, R. D., Suh, S. W., & Koh, J. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.092034699 · Cited by 432 · see citing works
The toxicity in vitro of β-amyloid protein
Iversen, L. L., Mortishire‐Smith, R. J., Pollack, S. J., & Shearman, M. S. (1995) · Biochemical Journal · doi:10.1042/bj3110001 · Cited by 425 · see citing works
Redox‐Active Metals, Oxidative Stress, and Alzheimer's Disease Pathology
HUANG, X., MOIR, R. D., TANZI, R. E., BUSH, A. I., & ROGERS, J. T. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1306.012 · Cited by 425 · see citing works
Self-citation
Movement of zinc and its functional significance in the brain
Takeda, A. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00044-8 · Cited by 416 · see citing works
Overview of mammalian zinc transporters
Kambe, T., Yamaguchi‐Iwai, Y., Sasaki, R., & Nagao, M. (2004) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-003-3148-y · Cited by 406 · see citing works
Metal ions and amyloid fiber formation in neurodegenerative diseases. Copper, zinc and iron in Alzheimer's, Parkinson's and prion diseases
Viles, J. H. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.05.003 · Cited by 403 · see citing works
Untangling amyloid-β, tau, and metals in Alzheimer's disease.
Savelieff, M. G., Lee, S., Liu, Y.-Z., & Lim, M. (2013) · ACS Chemical Biology · doi:10.1021/cb400080f · Cited by 368 · see citing works
Evidence that the β-Amyloid Plaques of Alzheimer's Disease Represent the Redox-silencing and Entombment of Aβ by Zinc
Cuajungco, M. P., Goldstein, L. E., Nunomura, A., Smith, M. A., Lim, J. T., Atwood, C., Huang, X., Farrag, Y. W., Perry, G. L., & Bush, A. I. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.c000165200 · Cited by 392 · see citing works
Self-citation
Structure of the Zinc Transporter YiiP
Lu, M., & Fu, D. (2007) · Science · doi:10.1126/science.1143748 · Cited by 386 · see citing works
Crosstalk between Nitric Oxide and Zinc Pathways to Neuronal Cell Death Involving Mitochondrial Dysfunction and p38-Activated K+ Channels
Bossy‐Wetzel, E., Talantova, M. V., Lee, W. D., Schölzke, M. N., Harrop, A., Mathews, E. A., Götz, T., Han, J., Ellisman, M. H., Perkins, G. A., et al. (2004) · Neuron · doi:10.1016/s0896-6273(04)00015-7 · Cited by 385 · see citing works
Copper Mediates Dityrosine Cross-Linking of Alzheimer's Amyloid-β
Atwood, C., Perry, G. L., Zeng, H., Kato, Y., Jones, W. D., Ling, K.-Q., Huang, X., Moir, R. D., Wang, D., Sayre, L. M., et al. (2003) · Biochemistry · doi:10.1021/bi0358824 · Cited by 371 · see citing works
Self-citation
Aggregation of Secreted Amyloid β-Protein into Sodium Dodecyl Sulfate-stable Oligomers in Cell Culture
Podlisny, M. B., Ostaszewski, B. L., Squazzo, S. L., Koo, E. H., Rydel, R. E., Teplow, D. B., & Selkoe, D. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.16.9564 · Cited by 364 · see citing works
Aluminium speciation in relation to aluminium bioavailability, metabolism and toxicity
Berthon, G. (2002) · Coordination Chemistry Reviews · doi:10.1016/s0010-8545(02)00021-8 · Cited by 366 · see citing works
Synaptically released zinc: Physiological functions and pathological effects
Frederickson, C. J., & Bush, A. I. (2001) · BioMetals · doi:10.1023/a:1012934207456 · Cited by 360 · see citing works
Self-citation
Mitochondrial Oxidative Stress Causes Hyperphosphorylation of Tau
Melov, S., Adlard, P. A., Morten, K., Johnson, F., Golden, T. R., Hinerfeld, D., Schilling, B., Mavros, C., Masters, C. L., Volitakis, I., et al. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000536 · Cited by 363 · see citing works
Self-citation
Role of Metal Ions in the Self-assembly of the Alzheimer’s Amyloid-β Peptide
Faller, P., Hureau, C., & Berthoumieu, O. (2013) · Inorganic Chemistry · doi:10.1021/ic4003059 · Cited by 355 · see citing works
Metallostasis in Alzheimer's disease
Ayton, S., Lei, P., & Bush, A. I. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.10.558 · Cited by 354 · see citing works
Self-citation
Metals and amyloid‐β in Alzheimer's disease
Maynard, C. J., Bush, A. I., Masters, C. L., Cappai, R., & Li, Q. (2005) · International Journal of Experimental Pathology · doi:10.1111/j.0959-9673.2005.00434.x · Cited by 353 · see citing works
Self-citation
Histochemically-reactive zinc in amyloid plaques, angiopathy, and degenerating neurons of Alzheimer's diseased brains
Suh, S. W., Jensen, K. B., Jensen, M. S., Silva, D. S., Kesslak, P. J., Danscher, G., & Frederickson, C. J. (2000) · Brain Research · doi:10.1016/s0006-8993(99)02096-x · Cited by 353 · see citing works
Overexpression of Alzheimer's Disease Amyloid-β Opposes the Age-dependent Elevations of Brain Copper and Iron
Maynard, C. J., Cappai, R., Volitakis, I., Cherny, R. A., White, A. R., Beyreuther, K. T., Masters, C. L., Bush, A. I., & Li, Q. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m204379200 · Cited by 352 · see citing works
Self-citation
Fibrillar β-Amyloid Induces Microglial Phagocytosis, Expression of Inducible Nitric Oxide Synthase, and Loss of a Select Population of Neurons in the Rat CNS<i>In Vivo</i>
Weldon, D. T., Rogers, S. D., Ghilardi, J. R., Finke, M. P., Cleary, J. P., O’Hare, E., Esler, W. P., Maggio, J. E., & Mantyh, P. W. (1998) · The Journal of Neuroscience · doi:10.1523/jneurosci.18-06-02161.1998 · Cited by 348 · see citing works
Implications of peptide assemblies in amyloid diseases
Ke, P. C., Sani, M., Ding, F., Käkinen, A., Javed, I., Separovic, F., Davis, T. P., & Mezzenga, R. (2017) · Chemical Society Reviews · doi:10.1039/c7cs00372b · Cited by 338 · see citing works
Copper(II)-induced self-oligomerization of α-synuclein
Paik, S. R., Shin, H.-J., Lee, J., Chang, C., & Kim, J. (1999) · Biochemical Journal · doi:10.1042/bj3400821 · Cited by 332 · see citing works
The Neurophysiology and Pathology of Brain Zinc
Sensi, S. L., Paoletti, P., Koh, J., Aizenman, E., Bush, A. I., & Hershfinkel, M. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.3454-11.2011 · Cited by 333 · see citing works
Self-citation
Medicinal Inorganic Chemistry Approaches to Passivation and Removal of Aberrant Metal Ions in Disease
Scott, L. E., & Orvig, C. (2009) · Chemical Reviews · doi:10.1021/cr9000176 · Cited by 332 · see citing works
The essential elements of Alzheimer’s disease
Lei, P., Ayton, S., & Bush, A. I. (2020) · Journal of Biological Chemistry · doi:10.1074/jbc.rev120.008207 · Cited by 336 · see citing works
Self-citation
Detection of single amyloid β-protein aggregates in the cerebrospinal fluid of Alzheimer's patients by fluorescence correlation spectroscopy
Pitschke, M., Prior, R., Haupt, M., & Riesner, D. (1998) · Nature Medicine · doi:10.1038/nm0798-832 · Cited by 326 · see citing works
Probing oxidative stress: Small molecule fluorescent sensors of metal ions, reactive oxygen species, and thiols
Hyman, L. M., & Franz, K. J. (2012) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2012.03.009 · Cited by 325 · see citing works
Link between Aluminum and the Pathogenesis of Alzheimer′s Disease: The Integration of the Aluminum and Amyloid Cascade Hypotheses
Kawahara, M., & Kato-Negishi, M. (2011) · International Journal of Alzheimer’s Disease · doi:10.4061/2011/276393 · Cited by 509 · see citing works
Mouse models of Alzheimer's disease
Hall, A. M., & Roberson, E. D. (2012) · Brain Research Bulletin · doi:10.1016/j.brainresbull.2011.11.017 · Cited by 317 · see citing works
Zinc-induced Alzheimer's Aβ1–40 Aggregation Is Mediated by Conformational Factors
Huang, X., Atwood, C., Moir, R. D., Hartshorn, M. A., Vonsattel, J., Tanzi, R. E., & Bush, A. I. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.42.26464 · Cited by 313 · see citing works
Self-citation
Metal complexing agents as therapies for Alzheimer’s disease
Bush, A. I. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00120-3 · Cited by 310 · see citing works
Self-citation
Solution structures of micelle-bound amyloid β-(1-40) and β-(1-42) peptides of Alzheimer’s disease 1 1Edited by P. E. Wright
Shao, H., Jao, S., Ma, K., & Zagorski, M. G. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1998.2348 · Cited by 308 · see citing works
A Novel Function of Monomeric Amyloid β-Protein Serving as an Antioxidant Molecule against Metal-Induced Oxidative Damage
Zou, K., Gong, J.-S., Yanagisawa, K., & Michikawa, M. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-12-04833.2002 · Cited by 305 · see citing works
Zinc ions promote Alzheimer Aβ aggregation via population shift of polymorphic states
Miller, Y., Ma, B., & Nussinov, R. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0913114107 · Cited by 304 · see citing works
Structural Changes of Region 1-16 of the Alzheimer Disease Amyloid β-Peptide upon Zinc Binding and in Vitro Aging
Zirah, S., Kozin, S. A., Mazur, A. K., Blond, A., Cheminant, M., Ségalas-Milazzo, I., Debey, P., & Rebuffat, S. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m504454200 · Cited by 304 · see citing works
Synthesis, optimization and applications of ZnO/polymer nanocomposites
Ponnamma, D., Cabibihan, J., Rajan, M., Pethaiah, S. S., Deshmukh, K., Gogoi, J. P., Pasha, S. K. K., Ahamed, M. B., Jagadish, K., Chandrashekar, B. N., et al. (2019) · Materials Science and Engineering C · doi:10.1016/j.msec.2019.01.081 · Cited by 307 · see citing works
The function of metallothionein
Vallée, B. L. (1995) · Neurochemistry International · doi:10.1016/0197-0186(94)00165-q · Cited by 301 · see citing works
Structure of Amyloid A4‐(1–40)‐Peptide of Alzheimer's Disease
Sticht, H., Bayer, P., Willbold, D., Dames, S. A., Hilbich, C., Beyreuther, K. T., Frank, R. W., & ROSCH, P. J. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.293_1.x · Cited by 300 · see citing works
Self-citation
Copper complexes of bis(thiosemicarbazones): from chemotherapeutics to diagnostic and therapeutic radiopharmaceuticals
Paterson, B. M., & Donnelly, P. S. (2011) · Chemical Society Reviews · doi:10.1039/c0cs00215a · Cited by 296 · see citing works
Selenium, selenoproteins and neurodegenerative diseases
Cardoso, B. R., Roberts, B. R., Bush, A. I., & Hare, D. J. (2015) · Metallomics · doi:10.1039/c5mt00075k · Cited by 295 · see citing works
Self-citation

Selective Aggregation of Endogenous β‐Amyloid Peptide and Soluble Amyloid Precursor Protein in Cerebrospinal Fluid by Zinc
Brown, A. M., Tummolo, D. M., Rhodes, K. J., Hofmann, J. R., Jacobsen, J. S., & Sonnenberg‐Reines, J. (1997) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1997.69031204.x · Cited by 55 · see citing works
The role of zinc in the cerebral deposition of A beta amyloid in Alzheimer's disease
Bush, A. I., & Re, T. (1995)
Self-citation
Role of Interaction between Zinc and Amyloid Beta in Pathogenesis of Alzheimer’s Disease
Kozin, S. A. (2023) · Biochemistry (Moscow) · doi:10.1134/s0006297923140055 · Cited by 15 · see citing works
Zinc‐Induced Aggregation of Human and Rat β‐Amyloid Peptides In Vitro
Esler, W. P., Stimson, E. R., Jennings, J. M., Ghilardi, J. R., Mantyh, P. W., & Maggio, J. E. (1996) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1996.66020723.x · Cited by 135 · see citing works
A novel zinc(II) binding site modulates the function of the beta A4 amyloid protein precursor of Alzheimer's disease
Bush, A. I., Multhaup, G., Moir, R. D., Williamson, T. G., Small, D. H., Rumble, B. A., Pollwein, P., Beyreuther, K. T., & Masters, C. L. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85394-2 · Cited by 286 · see citing works
Self-citation

Authors: Bush, A., Pettingell, W., Multhaup, G., d Paradis, M., Vonsattel, J., Gusella, J., Beyreuther, K., Masters, C., & Tanzi, R.
Affiliations: Harvard University (US)
Heidelberg University (DE)
Mental Health Research Institute (AU)
ORCID: Bush, A.
Multhaup, G
Gusella, J.
Masters, C.
Tanzi, R.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1994-09-02
Volume: 265
Issue: 5177
Pages: 1464-1467
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.8073293
OpenAlex: W2094808560
Cited by: 1,522
References: 31
Citations by year: 2026: 20 · 2025: 24 · 2024: 28 · 2023: 46 · 2022: 36 · 2021: 52 · 2020: 68 · 2019: 56 · 2018: 58 · 2017: 78 · 2016: 64 · 2015: 60 · 2014: 74 · 2013: 64 · 2012: 80
FWCI: 21.76
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (5r01ag011899-03, 5r01ns030428-07)
National Institute on Aging (R01 AG11899-01)
National Institute of Neurological Disorders and Stroke (R01 NS30428-03)
Topics: Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Keywords: Alzheimer's disease, Aβ40, zinc binding, amyloid fibril formation, zinc metabolism, cerebrospinal fluid, neuropathogenesis
MeSH terms: Alzheimer Disease, Animals, Brain, Edetic Acid, Humans, Kinetics, Peptide Fragments, Solubility, Zinc, Amyloid beta-Peptides, Mice, Rats

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

Rapid induction of Alzheimer A beta amyloid formation by zinc

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Related

Record

About these checks