Cited by 379Alzheimer's disease research and treatmentsTrace Elements in HealthDementia and Cognitive Impairment Research

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Alzheimer's disease, metal ions and metal homeostatic therapy

Zatta, Paolo, Drago, Denise, Bolognin, Silvia, Sensi, Stefano L.·2009·Trends in Pharmacological Sciences

DOI 10.1016/j.tips.2009.05.002

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Abstract

Mounting evidences support the idea that endogenous 'biometals', such as copper, iron, zinc and exogenous ones such as aluminum, can be involved as factors or cofactors in the etiopathogenesis of a variety of neurodegenerative diseases. Alzheimer's disease (AD) is a multifactorial neurodegenerative condition associated with pathological accumulation of amyloid plaques and with the appearance of deposit of neurofibrillary tangles. In AD, the process of beta-amyloid (Abeta) misfolding and plaque aggregation is greatly influenced by alterations in the homeostasis of the aforementioned metal ions. Here, we discuss the most recent evidences that associate metal ion dyshomeostasis with the development of AD. As for aluminum, a role for this ion in AD pathogenesis is still controversial. Thus, here, we also critically review new findings that argue for and against the 'aluminum hypothesis'. Finally, it is discussed how therapeutic strategies aimed at restoring metal homeostasis can delay and modify the progression of AD-related neurodegeneration.

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1 retracted

RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769
Retracted
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
Alzheimer's disease: the amyloid cascade hypothesis
Hardy, J. A., & Higgins, G. A. (1992) · Science · doi:10.1126/science.1566067 · Cited by 7,484
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126
The Free Radical Theory of Aging Matures
BECKMAN, K. B., & AMES, B. N. (1998) · Physiological Reviews · doi:10.1152/physrev.1998.78.2.547 · Cited by 3,879
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
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942
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
Natural oligomers of the amyloid-β protein specifically disrupt cognitive function
Cleary, J. P., Walsh, D. M., Hofmeister, J. J., Shankar, G. M., Kuskowski, M. A., Selkoe, D. J., & Ashe, K. H. (2004) · Nature Neuroscience · doi:10.1038/nn1372 · Cited by 1,722
The Dialysis Encephalopathy Syndrome
Alfrey, A. C., LeGendre, G. R., & Kaehny, W. D. (1976) · New England Journal of Medicine · doi:10.1056/nejm197601222940402 · Cited by 1,628
Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP
Lewis, J., Dickson, D. W., Lin, W.-L., Chisholm, L., Corral, A., Jones, G., Yen, S.-H., Sahara, N., Skipper, L., Yager, D., et al. (2001) · Science · doi:10.1126/science.1058189 · Cited by 1,611
Formation of Neurofibrillary Tangles in P301L Tau Transgenic Mice Induced by Aβ42 Fibrils
Götz, J., Chen, F., van Dorpe, J., & Nitsch, R. M. (2001) · Science · doi:10.1126/science.1062097 · Cited by 1,526
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
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
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
Calcium Dysregulation and Membrane Disruption as a Ubiquitous Neurotoxic Mechanism of Soluble Amyloid Oligomers*♦
Demuro, A., Mina, E. W., Kayed, R., Milton, S. C. F., Parker, I., & Glabe, C. G. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m500997200 · Cited by 1,057
Intraneuronal Aβ42 Accumulation in Human Brain
Gouras, G. K., Tsai, J., Naslund, J., Vincent, B., Edgar, M., Checler, F., Greenfield, J. P., Haroutunian, V., Buxbaum, J. D., Xu, H., et al. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64700-1 · Cited by 991
Metal-Protein Attenuation With Iodochlorhydroxyquin (Clioquinol) Targeting Aβ Amyloid Deposition and Toxicity in Alzheimer Disease: A Pilot Phase 2 Clinical Trial
Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q.-X., Tammer, A., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.12.1685 · Cited by 988
Alzheimer's Disease: X-Ray Spectrometric Evidence of Aluminum Accumulation in Neurofibrillary Tangle-Bearing Neurons
Perl, D. P., & Brody, A. R. (1980) · Science · doi:10.1126/science.7367858 · Cited by 985
Tau phosphorylation: the therapeutic challenge for neurodegenerative disease
Hanger, D. P., Anderton, B. H., & Noble, W. (2009) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2009.01.003 · Cited by 965
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
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
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
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
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 587
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 582
Alzheimer's disease – do tauists and baptists finally shake hands?
Mudher, A. K., & Lovestone, S. (2002) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)02031-2 · Cited by 523
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 466
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
The Function of Zinc Metallothionein: A Link between Cellular Zinc and Redox State
Maret, W. (2000) · Journal of Nutrition · doi:10.1093/jn/130.5.1455s · Cited by 417
Preferential Zn 2+ influx through Ca 2+ -permeable AMPA/kainate channels triggers prolonged mitochondrial superoxide production
Sensi, S. L., Yin, H. Z., Carriedo, S. G., Rao, S. S., & Weiss, J. H. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.5.2414 · Cited by 408
Self-citation
Modulation of mitochondrial function by endogenous Zn 2+ pools
Sensi, S. L., Ton-That, D., Sullivan, P. G., Jonas, E. A., Gee, K. R., Kaczmarek, L. K., & Weiss, J. H. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1031598100 · Cited by 406
Self-citation
The Oligomerization of Amyloid β-Protein Begins Intracellularly in Cells Derived from Human Brain
Walsh, D. M., Tseng, B. P., Rydel, R. E., Podlisny, M. B., & Selkoe, D. J. (2000) · Biochemistry · doi:10.1021/bi001048s · Cited by 401
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
Matrix Metalloproteinases Expressed by Astrocytes Mediate Extracellular Amyloid-β Peptide Catabolism
Yin, K.-J., Cirrito, J. R., Yan, P., Hu, X., Xiao, Q., Pan, X., Bateman, R., Song, H., Hsu, F.-F., Turk, J., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.2085-06.2006 · Cited by 381
Temporal Profile of Amyloid-β (Aβ) Oligomerization in an in Vivo Model of Alzheimer Disease
Oddo, S., Caccamo, A., Tran, L., Lambert, M. P., Glabe, C. G., Klein, W. L., & LaFerla, F. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m507892200 · Cited by 379
Induction of Neuronal Apoptosis by Thiol Oxidation
Aizenman, E., Stout, A. K., Hartnett, K. A., Dineley, K. E., McLaughlin, B., & Reynolds, I. J. (2000) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2000.0751878.x · Cited by 376
Regional distribution of iron and iron‐regulatory proteins in the brain in aging and Alzheimer's disease
Connor, J. R., Snyder, B. S., Beard, J. L., Fine, R. E., & Mufson, E. J. (1992) · Journal of Neuroscience Research · doi:10.1002/jnr.490310214 · Cited by 374
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
The role of metals in neurodegenerative processes: aluminum, manganese, and zinc
Zatta, P. F., Lucchini, R. G., van Rensburg, S. J., & Taylor, A. (2003) · Brain Research Bulletin · doi:10.1016/s0361-9230(03)00182-5 · Cited by 344
Self-citation
Dietary Cu stabilizes brain superoxide dismutase 1 activity and reduces amyloid Aβ production in APP23 transgenic mice
Bayer, T. A., Schäfer, S., Simons, A., Kemmling, A., Kamer, T., Tepest, R., Eckert, A., Schüssel, K., Eikenberg, O., Sturchler, C., et al. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2332818100 · Cited by 329
Metals and Alzheimer's disease
Adlard, P. A., & Bush, A. I. (2006) · Journal of Alzheimer's Disease · doi:10.3233/jad-2006-102-303 · Cited by 324
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
Expression of monocarboxylate transporter MCT1 by brain endothelium and glia in adult and suckling rats
Gerhart, D. Z., Enerson, B. E., Zhdankina, O., Leino, R. L., & Drewes, L. R. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.1.e207 · Cited by 300
Reduction of Soluble Aβ and Tau, but Not Soluble Aβ Alone, Ameliorates Cognitive Decline in Transgenic Mice with Plaques and Tangles
Oddo, S., Vasilevko, V., Caccamo, A., Kitazawa, M., Cribbs, D. H., & LaFerla, F. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608485200 · Cited by 298
Aluminium in Alzheimer?s disease: are we still at a crossroad?
Gupta, V. B., Anitha, S., Hegde, M. L., Zecca, L., Garruto, R. M., Ravid, R., Shankar, S. K., Stein, R., Shanmugavelu, P., & Rao, K. S. J. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-004-4317-3 · Cited by 294
NMDA Receptor Activation Mediates Copper Homeostasis in Hippocampal Neurons
Schlief, M. L., Craig, A. M., & Gitlin, J. D. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3699-04.2005 · Cited by 291
Increasing Cu bioavailability inhibits Aβ oligomers and tau phosphorylation
Crouch, P. J., Hung, L. W., Adlard, P. A., Cortés, M., Lal, V., Filiz, G., Perez, K. A., Nurjono, M., Caragounis, A., Du, T., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0809057106 · Cited by 288
Copper levels are increased in the cerebral cortex and liver of APP and APLP2 knockout mice
White, A. R., Reyes, R., Mercer, J. F. B., Camakaris, J., Zheng, H., Bush, A. I., Multhaup, G., Beyreuther, K. T., Masters, C. L., & Cappai, R. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01861-2 · Cited by 287
Degradation of the Alzheimer Disease Amyloid β-Peptide by Metal-dependent Up-regulation of Metalloprotease Activity
White, A. R., Du, T., Laughton, K. M., Volitakis, I., Sharples, R. A., Xilinas, M. E., Hoke, D. E., Holsinger, R. M. D., Evin, G., Cherny, R. A., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m602487200 · Cited by 284
Discussion
Lovestone, S., & Reynolds, C. H. (1997) · Neuroscience · doi:10.1016/s0306-4522(96)00577-5 · Cited by 278
Effects of aluminum on the nervous system and its possible link with neurodegenerative diseases
Kawahara, M. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8210 · Cited by 268
Mechanisms of Aβ mediated neurodegeneration in Alzheimer's disease
Crouch, P. J., Harding, S.-M. E., White, A. R., Camakaris, J., Bush, A. I., & Masters, C. L. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.07.013 · Cited by 254
Absence of aluminium in neuritic plaque cores in Alzheimer's disease
Landsberg, J., Mcdonald, B., & Watt, F. (1992) · Nature · doi:10.1038/360065a0 · Cited by 254
The βA4 amyloid precursor protein binding to copper
Hesse, L., Beher, D., Masters, C. L., & Multhaup, G. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)00658-x · Cited by 247
Blood-brain barrier flux of aluminum, manganese, iron and other metals suspected to contribute to metal-induced neurodegeneration
Yokel, R. A. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-102-309 · Cited by 246
A Role for Synaptic Zinc in Activity-Dependent Aβ Oligomer Formation and Accumulation at Excitatory Synapses
Deshpande, A., Kawai, H., Metherate, R., Glabe, C. G., & Busciglio, J. (2009) · The Journal of Neuroscience · doi:10.1523/jneurosci.5980-08.2009 · Cited by 232
Metal Ions Differentially Influence the Aggregation and Deposition of Alzheimer's β-Amyloid on a Solid Template
Ha, C., Ryu, J., & Park, C. B. (2007) · Biochemistry · doi:10.1021/bi7000032 · Cited by 231
Aluminum access to the brain: a role for transferrin and its receptor.
Roskams, A. J., & Connor, J. R. (1990) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.87.22.9024 · Cited by 230
Gradual Alteration of Mitochondrial Structure and Function by β-Amyloids: Importance of Membrane Viscosity Changes, Energy Deprivation, Reactive Oxygen Species Production, and Cytochrome c Release
Aleardi, A. M., Benard, G., Augereau, O., Malgat, M., Talbot, J.-C., Mazat, J., Letellier, T., Dachary-Prigent, J., Solaini, G., & Rossignol, R. (2005) · Journal of Bioenergetics and Biomembranes · doi:10.1007/s10863-005-6631-3 · Cited by 227
Zinc-Containing Neurons
Frederickson, C. J., & Moncrieff, D. W. (1994) · Neurosignals · doi:10.1159/000109536 · Cited by 223
The Alzheimer's Disease Amyloid Precursor Protein Modulates Copper-Induced Toxicity and Oxidative Stress in Primary Neuronal Cultures
White, A. R., Multhaup, G., Maher, F., Bellingham, S. A., Camakaris, J., Zheng, H., Bush, A. I., Beyreuther, K., Masters, C. L., & Cappai, R. (1999) · Journal of Neuroscience · doi:10.1523/jneurosci.19-21-09170.1999 · Cited by 220
The lipophilic metal chelator DP-109 reduces amyloid pathology in brains of human β-amyloid precursor protein transgenic mice
Lee, J., Friedman, J. E., Angel, I., Kozak, A., & Koh, J. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2004.01.005 · Cited by 190
Role of the Menkes copper-transporting ATPase in NMDA receptor-mediated neuronal toxicity
Schlief, M. L., West, T., Craig, A. M., Holtzman, D. M., & Gitlin, J. D. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0605390103 · Cited by 187
The functional significance of brain metallothioneins
Aschner, M. (1996) · The FASEB Journal · doi:10.1096/fasebj.10.10.8751715 · Cited by 182
In vivo and in vitro effects of aluminum on the activity of mouse brain acetylcholinesterase
Zatta, P. F., Ibn-Lkhayat-Idrissi, M., Zambenedetti, P., Kilyén, M., & Kiss, T. (2002) · Brain Research Bulletin · doi:10.1016/s0361-9230(02)00836-5 · Cited by 170
Self-citation
Orally available compound prevents deficits in memory caused by the Alzheimer amyloid‐β oligomers
Townsend, M., Cleary, J. P., Mehta, T., Hofmeister, J. J., Lesné, S., O‘Hare, E., Walsh, D. M., & Selkoe, D. J. (2006) · Annals of Neurology · doi:10.1002/ana.21051 · Cited by 169
Zinc released from metallothionein-iii may contribute to hippocampal CA1 and thalamic neuronal death following acute brain injury
Lee, J., Kim, J.-H., Palmiter, R. D., & Koh, J. (2003) · Experimental Neurology · doi:10.1016/s0014-4886(03)00382-0 · Cited by 166
Rethinking the Excitotoxic Ionic Milieu:The Emerging Role of Zn 2+ in Ischemic Neuronal Injury
Sensi, S. L., & Jeng, J. (2004) · Current Molecular Medicine · doi:10.2174/1566524043479211 · Cited by 160
Self-citation
AMPA/kainate receptor‐triggered Zn2+ entry into cortical neurons induces mitochondrial Zn2+ uptake and persistent mitochondrial dysfunction
Sensi, S. L., Yin, H. Z., & Weiss, J. H. (2000) · European Journal of Neuroscience · doi:10.1046/j.1460-9568.2000.00277.x · Cited by 158
Self-citation
Pyrrolidine Dithiocarbamate Activates Akt and Improves Spatial Learning in APP/PS1 Mice without Affecting β-Amyloid Burden
Malm, T., Iivonen, H., Goldsteins, G., Keksa-Goldsteine, V., Ahtoniemi, T., Kanninen, K. M., Salminen, A., Auriola, S. O. K., van Groen, T., Tanila, H., et al. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.0059-07.2007 · Cited by 157
Zinc and 4-Hydroxy-2-Nonenal Mediate Lysosomal Membrane Permeabilization Induced by H2O2in Cultured Hippocampal Neurons
Hwang, J. J., Lee, S.-J., Kim, T.-Y., Cho, J.-H., & Koh, J. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0199-08.2008 · Cited by 153
Metal exposure and Alzheimer’s pathogenesis
Liu, G., Huang, W., Moir, R. D., Vanderburg, C. R., Lai, B. C. H., Peng, Z., Tanzi, R. E., Rogers, J. T., & Huang, X. (2006) · Journal of Structural Biology · doi:10.1016/j.jsb.2005.12.011 · Cited by 135
Laser microprobe analysis of brain aluminum in Alzheimer' disease
Lovell, M. A., Ehmann, W., & Markesbery, W. (1993) · Annals of Neurology · doi:10.1002/ana.410330107 · Cited by 130
Redox Silencing of Copper in Metal-linked Neurodegenerative Disorders
Meloni, G., Faller, P., & Vaša´k, M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m701357200 · Cited by 130
Aluminum-triggered structural modifications and aggregation of β-amyloids
Ricchelli, F., Drago, D., Filippi, B., Tognon, G., & Zatta, P. F. (2005) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-005-5141-0 · Cited by 128
Self-citation
Aluminum modifies the properties of Alzheimer's disease PHF tau proteins in vivo and in vitro
Shin, R. W., Lee, V., & Trojanowski, J. Q. (1994) · Journal of Neuroscience · doi:10.1523/jneurosci.14-11-07221.1994 · Cited by 126
Sequestration of Copper from β-Amyloid Promotes Selective Lysis by Cyclen-Hybrid Cleavage Agents
Wu, W., Lei, P., Liu, Q. R., Hu, J., Gunn, A. P., Chen, M., Rui, Y., Su, X., Xie, Z., Zhao, Y., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m804722200 · Cited by 124
The galvanization of β-amyloid in Alzheimer's disease
Bush, A. I., & Tanzi, R. E. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.122249699 · Cited by 122
A Laser Microprobe Mass Analysis of Brain Aluminum and Iron in Dementia pugilistica: Comparison with Alzheimer's Disease
Bouras, C., Giannakopoulos, P., Good, P. F., Hsu, A., Hof, P. R., & Perl, D. P. (2007) · European Neurology · doi:10.1159/000112903 · Cited by 112
Aluminum complexing enhances amyloid β protein penetration of blood–brain barrier
Banks, W. A., Niehoff, M. L., Drago, D., & Zatta, P. F. (2006) · Brain Research · doi:10.1016/j.brainres.2006.07.112 · Cited by 104
Self-citation
Boutons Containing Vesicular Zinc Define a Subpopulation of Synapses with Low AMPAR Content in Rat Hippocampus
Sindreu, C. B. (2003) · Cerebral Cortex · doi:10.1093/cercor/13.8.823 · Cited by 103
Distribution of histochemically reactive zinc in the forebrain of the rat
Frederickson, C. J., Rampy, B. A., Reamy-Rampy, S., & Howell, G. A. (1992) · Journal of Chemical Neuroanatomy · doi:10.1016/0891-0618(92)90007-d · Cited by 102
Brain Iron Metabolism and Neurodegenerative Disorders
Sipe, J. C., Lee, P. L., & Beutler, E. (2002) · Developmental Neuroscience · doi:10.1159/000065701 · Cited by 94
Direct visualization of mitochondrial zinc accumulation reveals uniporter‐dependent and ‐independent transport mechanisms
Malaiyandi, L. M., Vergun, O. V., Dineley, K. E., & Reynolds, I. J. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03116.x · Cited by 93
The distribution of aluminum into and out of the brain
Yokel, R. A., Allen, D. D., & Ackley, D. C. (1999) · Journal of Inorganic Biochemistry · doi:10.1016/s0162-0134(99)00124-5 · Cited by 91
Copper reduction by copper binding proteins and its relation to neurodegenerative diseases
Opazo, C., Barría, M. I., Ruiz, F. H., & Inestrosa, N. C. (2003) · BioMetals · doi:10.1023/a:1020795422185 · Cited by 83
Potential pathogenic role of β-amyloid1–42–aluminum complex in Alzheimer's disease
Drago, D., Bettella, M., Bolognin, S., Cendron, L., Ščančar, J., Milačić, R., Ricchelli, F., Casini, A., Luigi Messori, A., Tognon, G., et al. (2007) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2007.10.014 · Cited by 82
Self-citation
Absorption of Aluminium-26 in Alzheimer’s Disease, Measured Using Accelerator Mass Spectrometry
Moore, P. B., Day, J., Taylor, G. A., Ferrier, I. N., Fifield, L. K., & Edwardson, J. A. (2000) · Dementia and Geriatric Cognitive Disorders · doi:10.1159/000017216 · Cited by 81
Depletion of Intracellular Zinc from Neurons by Use of an Extracellular Chelator In Vivo and In Vitro
Frederickson, C. J., Suh, S. W., Koh, J., Yoo, K., Thompson, R. B., LaBuda, C. J., Balaji, R. V., & Cuajungco, M. P. (2002) · Journal of Histochemistry & Cytochemistry · doi:10.1177/002215540205001210 · Cited by 81
The modulation of metal bio‐availability as a therapeutic strategy for the treatment of Alzheimer's disease
Crouch, P. J., White, A. R., & Bush, A. I. (2007) · FEBS Journal · doi:10.1111/j.1742-4658.2007.05918.x · Cited by 78
Aluminum and Alzheimer's disease, a personal perspective after 25 years
Perl, D. P., & Moalem, S. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-9s332 · Cited by 74
Aluminum Modulates Effects of β Amyloid 1–42 on Neuronal Calcium Homeostasis and Mitochondria Functioning and Is Altered in a Triple Transgenic Mouse Model of Alzheimer's Disease
Drago, D., Cavaliere, A., Mascetra, N., Ciavardelli, D., Ilio, C. D., Zatta, P. F., & Sensi, S. L. (2008) · Rejuvenation Research · doi:10.1089/rej.2008.0761 · Cited by 74
Self-citation
Is Zn2+ transported by the mitochondrial calcium uniporter?
Saris, N.-E. L., & Niva, K. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01256-3 · Cited by 74
Aluminum citrate uptake by immortalized brain endothelial cells: implications for its blood–brain barrier transport
Yokel, R. A., Wilson, M. C., Harris, W. R., & Halestrap, A. P. (2002) · Brain Research · doi:10.1016/s0006-8993(02)02234-5 · Cited by 64
Zinc-bound metallothioneins as potential biological markers of ageing
Mocchegiani, E., Giacconi, R., Cipriano, C., Muzzioli, M., Fattoretti, P., Bertoni–Freddari, C., Isani, G., Zambenedetti, P., & Zatta, P. F. (2001) · Brain Research Bulletin · doi:10.1016/s0361-9230(01)00468-3 · Cited by 64
Self-citation
The variations during the circadian cycle of liver CD1d-unrestricted NK1.1+TCRγ/δ+ cells lead to successful ageing. Role of metallothionein/IL-6/gp130/PARP-1 interplay in very old mice
Mocchegiani, E., Giacconi, R., Cipriano, C., Gasparini, N., Bernardini, G., Malavolta, M., Menegazzi, M., Cavalieri, E., Muzzioli, M., Ciampa, A. R., et al. (2004) · Experimental Gerontology · doi:10.1016/j.exger.2004.01.014 · Cited by 54
Mechanisms of aluminum absorption in rats
Whitehead, M. W., Farrar, G., CHRISTIE, G. L., Blair, J., Thompson, R., & Powell, J. J. (1997) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/65.5.1446 · Cited by 53
Elevated Zinc Transporter-6 in Mild Cognitive Impairment, Alzheimer Disease, and Pick Disease
Lovell, M. A., Smith, J. L., & Markesbery, W. R. (2006) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/01.jnen.0000229237.98124.91 · Cited by 51
Altered oxidant-mediated intraneuronal zinc mobilization in a triple transgenic mouse model of Alzheimer’s disease
Sensi, S. L., Rapposelli, I. G., Frazzini, V., & Mascetra, N. (2007) · Experimental Gerontology · doi:10.1016/j.exger.2007.10.018 · Cited by 49
Self-citation
Dialysis Encephalopathy
Kerr, D. N. S., Ward, M. K., & Parkinson, I. S. (1985) · Springer eBooks · doi:10.1007/978-1-4684-4826-9_19 · Cited by 49
Aluminum(III) influences the permeability of the blood-brain barrier to [14C]sucrose in rats
Favarato, M., Zatta, P. F., Perazzolo, M., Fontana, L., & Nicolini, M. (1992) · Brain Research · doi:10.1016/0006-8993(92)90647-r · Cited by 48
Self-citation
Comparative Effects of Aβ(1-42)-Al Complex from Rat and Human Amyloid on Rat Endothelial Cell Cultures
Drago, D., Folin, M., Baiguera, S., Tognon, G., Ricchelli, F., & Zatta, P. F. (2007) · Journal of Alzheimer s Disease · doi:10.3233/jad-2007-11107 · Cited by 42
Self-citation
Neurofibrillary pathology and aluminum in Alzheimer's disease.
Shin, R., Lee, V. M., & Trojanowski, J. Q. (1995) · PubMed · Cited by 36
Involvement of amyloid β precursor protein (AβPP) modulated copper homeostasis in Alzheimer's disease
Bayer, T. A., & Multhaup, G. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8212 · Cited by 32
Aluminium in Alzheimer's?
Good, P. F., & Perl, D. P. (1993) · Nature · doi:10.1038/362418b0 · Cited by 29
1,1′-Xylyl bis-1,4,8,11-tetraaza cyclotetradecane: A new potential copper chelator agent for neuroprotection in Alzheimer’s disease. Its comparative effects with clioquinol on rat brain copper distribution
Moret, V., Laras, Y., Pietrancosta, N., Garino, C., Quéléver, G., Rolland, A., Mallet, B., Norreel, J.-C., & Kraus, J. (2006) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2006.03.026 · Cited by 29
Argyrophilic inclusions distinct from Alzheimer neurofibrillary changes in one case of dialysis-associated encephalopathy
Reusche, E. (1997) · Acta Neuropathologica · doi:10.1007/s004010050757 · Cited by 26
Interrelationships among brain, endocrine and immune response in ageing and successful ageing: role of metallothionein III isoform
Giacconi, R., Cipriano, C., Muzzioli, M., Gasparini, N., Orlando, F., & Mocchegiani, E. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00011-3 · Cited by 22
Aluminium leaching from utensils — a kinetic study
Rao, K. S. J., & Rao, G. V. (1995) · International Journal of Food Sciences and Nutrition · doi:10.3109/09637489509003383 · Cited by 22
A fatal case of aluminium encephalopathy in a patient with severe chronic renal failure not on dialysis
Zatta, P. F. (2004) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/gfh439 · Cited by 21
Self-citation
Aluminum and Alzheimer's disease: A Vexata Questio between uncertain data and a lot of imagination
Zatta, P. F. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-10106 · Cited by 17
Self-citation
Mutual Stimulation of Beta-Amyloid Fibrillogenesis by Clioquinol and Divalent Metals
Bolognin, S., Zatta, P. F., Drago, D., Parnigotto, P. P., Ricchelli, F., & Tognon, G. (2008) · NeuroMolecular Medicine · doi:10.1007/s12017-008-8046-x · Cited by 16
Self-citation
Interactions of β‐Amyloids with the Blood–Brain Barrier
Banks, W. A., Kastin, A. J., Maness, L. M., BANKS, M. F., Shayo, M., & McLay, R. N. (1997) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1997.tb48470.x · Cited by 16
Aluminium Administered in Drinking Water but not in the Diet Influences Biopterin Metabolism in the Rodent
AMSTRONG, R. A., Anderson, J., Cowburn, J. D., Juliette, C. O. X., & Blair, J. A. (1992) · Biological Chemistry Hoppe-Seyler · doi:10.1515/bchm3.1992.373.2.1075 · Cited by 16
Untitled work
(1998) · PubMed

Research works printed but not linked: 1

Lovestone, 1997, The phosphorylation of tau: a critical stage in neurodevelopment and neurodegenerative processes, Neuroscience, 78, 309

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Authors: Zatta, P., Drago, D., Bolognin, S., & Sensi, S. L.
Affiliations: University of Padua (IT)
University of California, Irvine (US)
Corresponding author: Zatta, Paolo
Sensi, Stefano L.
ORCID: Drago, Denise
Bolognin, Silvia
Sensi, Stefano L.
Venue: Trends in Pharmacological Sciences
Publisher: Elsevier BV
Published: 2009-07
Volume: 30
Issue: 7
Pages: 346-355
ISSN: 0165-6147 (ISSN-L)
DOI: 10.1016/j.tips.2009.05.002
OpenAlex: W2025615265
Cited by: 369
References: 118
Citations by year: 2026: 11 · 2025: 11 · 2024: 23 · 2023: 22 · 2022: 18 · 2021: 15 · 2020: 24 · 2019: 19 · 2018: 21 · 2017: 17 · 2016: 25 · 2015: 13 · 2014: 28 · 2013: 19 · 2012: 29
FWCI: 3.72
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Trends in Pharmacological Sciences (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Health Sciences › Nursing › Nutrition and Dietetics › Trace Elements in Health
Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords: Alzheimer's disease, metal ions, metal homeostasis, copper, iron, zinc, aluminum, amyloid plaques, neurofibrillary tangles, neurodegeneration
MeSH terms: Alzheimer Disease, Animals, Homeostasis, Humans, Clioquinol, Metals, Plaque, Amyloid

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Alzheimer's disease, metal ions and metal homeostatic therapy

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