Cited by 590Alzheimer's disease research and treatmentsNeuroscience and Neuropharmacology ResearchNeuroinflammation and Neurodegeneration Mechanisms

The DOI matches its Crossref record; 109 of the 109 references it cites were found in a registry or an index.

Amyloid beta oligomers induce impairment of neuronal insulin receptors

Zhao, Wei‐Qin, De Felice, Fernanda G., Fernandez, Sara, Chen, Hui, Lambert, Mary P., Quon, Michael J., Krafft, Grant A., Klein, William L.·2008·The FASEB Journal

DOI 10.1096/fj.06-7703com

Open this paper in CoChat — free account

Abstract

Recent studies have indicated an association between Alzheimer's disease (AD) and central nervous system (CNS) insulin resistance. However, the cellular mechanisms underlying the link between these two pathologies have not been elucidated. Here we show that signal transduction by neuronal insulin receptors (IR) is strikingly sensitive to disruption by soluble Abeta oligomers (also known as ADDLs). ADDLs are known to accumulate in AD brain and have recently been implicated as primary candidates for initiating deterioration of synapse function, composition, and structure. Using mature cultures of hippocampal neurons, a preferred model for studies of synaptic cell biology, we found that ADDLs caused a rapid and substantial loss of neuronal surface IRs specifically on dendrites bound by ADDLs. Removal of dendritic IRs was associated with increased receptor immunoreactivity in the cell body, indicating redistribution of the receptors. The neuronal response to insulin, measured by evoked IR tyrosine autophosphorylation, was greatly inhibited by ADDLs. Inhibition also was seen with added glutamate or potassium-induced depolarization. The effects on IR function were completely blocked by NMDA receptor antagonists, tetrodotoxin, and calcium chelator BAPTA-AM. Downstream from the IR, ADDLs induced a phosphorylation of Akt at serine473, a modification associated with neurodegenerative and insulin resistance diseases. These results identify novel factors that affect neuronal IR signaling and suggest that insulin resistance in AD brain is a response to ADDLs, which disrupt insulin signaling and may cause a brain-specific form of diabetes as part of an overall pathogenic impact on CNS synapses.

Integrity signals

Registry

Crossref · 10.1096/fj.06-7703com

Cites

109 of 109 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?

Alzheimer's Disease Is a Synaptic Failure
Selkoe, D. J. (2002) · Science · doi:10.1126/science.1074069 · Cited by 4,420
Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
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
Self-citation
Pathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052
Critical nodes in signalling pathways: insights into insulin action
Taniguchi, C. M., Emanuelli, B., & Kahn, C. R. (2006) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1837 · Cited by 2,760
AMPA Receptor Trafficking and Synaptic Plasticity
Malinow, R., & Malenka, R. C. (2002) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.25.112701.142758 · Cited by 2,588
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
Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease – is this type 3 diabetes?
Steen, E., Terry, B. M., J. Rivera, E., Cannon, J. L., Neely, T. R., Tavares, R., Xu, X. J., Wands, J. R., & de la Monte, S. M. (2005) · Journal of Alzheimer's Disease · doi:10.3233/jad-2005-7107 · Cited by 1,703
Regulation of NMDA receptor trafficking by amyloid-β
Snyder, E. M., Nong, Y., Almeida, C. G., Paul, S., Moran, T., Choi, E. Y., Nairn, A. C., Salter, M. W., Lombroso, P. J., Gouras, G. K., et al. (2005) · Nature Neuroscience · doi:10.1038/nn1503 · Cited by 1,561 · cited 3×
“The redistribution of IRs is consistent with reports in which other proteins important for synaptic plasticity, including NMDA receptor subunits and EphB2 receptor tyrosine kinase, also show surface loss caused by soluble forms of A (56, 69).”
Deciphering the Molecular Basis of Memory Failure in Alzheimer's Disease
Walsh, D. M., & Selkoe, D. J. (2004) · Neuron · doi:10.1016/j.neuron.2004.09.010 · Cited by 1,207
Aβ Oligomer-Induced Aberrations in Synapse Composition, Shape, and Density Provide a Molecular Basis for Loss of Connectivity in Alzheimer's Disease
Lacor, P. N., Buniel, M. C., Furlow, P. W., Sanz Clemente, A., Velasco, P. T., Wood, M., Viola, K. L., & Klein, W. L. (2007) · The Journal of Neuroscience · doi:10.1523/jneurosci.3501-06.2007 · Cited by 1,188
Self-citation
Alzheimer's disease-affected brain: Presence of oligomeric Aβ ligands (ADDLs) suggests a molecular basis for reversible memory loss
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
Self-citation
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
Receptor trafficking and synaptic plasticity
Collingridge, G. L., Isaac, J. T. R., & Wang, Y. T. (2004) · Nature Reviews Neuroscience · doi:10.1038/nrn1556 · Cited by 1,046
AMPAR Removal Underlies Aβ-Induced Synaptic Depression and Dendritic Spine Loss
Hsieh, H., Boehm, J., Sato, C., Iwatsubo, T., Tomita, T., Sisodia, S., & Malinow, R. (2006) · Neuron · doi:10.1016/j.neuron.2006.10.035 · Cited by 1,042
Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action
Aguirre, V., Werner, E. D., Giraud, J., Lee, Y. H., Shoelson, S. E., & White, M. F. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m101521200 · Cited by 1,010
Targeting small Aβ oligomers: the solution to an Alzheimer's disease conundrum?
Klein, W. (2001) · Trends in Neurosciences · doi:10.1016/s0166-2236(00)01749-5 · Cited by 989
Synaptic Targeting by Alzheimer's-Related Amyloid β Oligomers
Lacor, P. N., Buniel, M. C., Chang, L., Fernandez, S. J., Gong, Y., Viola, K. L., Lambert, M. P., Velasco, P. T., Bigio, E. H., Finch, C. E., et al. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.3432-04.2004 · Cited by 954
Self-citation
Signaling pathways in insulin action: molecular targets of insulin resistance
Pessin, J. E., & Saltiel, A. R. (2000) · Journal of Clinical Investigation · doi:10.1172/jci10582 · Cited by 939
Paradigm shift in neuroprotection by NMDA receptor blockade: memantine and beyond
Lipton, S. A. (2006) · Nature Reviews Drug Discovery · doi:10.1038/nrd1958 · Cited by 909
Aβ Oligomers Induce Neuronal Oxidative Stress through an N-Methyl-D-aspartate Receptor-dependent Mechanism That Is Blocked by the Alzheimer Drug Memantine
De Felice, F. G., Velasco, P. T., Lambert, M. P., Viola, K., Fernandez, S. J., Ferreira, S. T., & Klein, W. L. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m607483200 · Cited by 882
Self-citation
Nanoparticle-based detection in cerebral spinal fluid of a soluble pathogenic biomarker for Alzheimer’s disease
Georganopoulou, D. G., Chang, L., Nam, J.-M., Thaxton, C. S., Mufson, E. J., Klein, W. L., & Mirkin, C. A. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0409336102 · Cited by 835
Insulin and neurodegenerative disease: shared and specific mechanisms
Craft, S., & Stennis Watson, G. (2004) · The Lancet Neurology · doi:10.1016/s1474-4422(04)00681-7 · Cited by 830
Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking
Chowdhury, S., Shepherd, J. D., Okuno, H., Lyford, G., Petralia, R. S., Plath, N., Kuhl, D., Huganir, R. L., & Worley, P. F. (2006) · Neuron · doi:10.1016/j.neuron.2006.08.033 · Cited by 792
Inflammatory pathways and insulin action
Hotamisligil, G. S. (2003) · International Journal of Obesity · doi:10.1038/sj.ijo.0802502 · Cited by 717
FROM MICE TO MEN: Insights into the Insulin Resistance Syndromes
Biddinger, S. B., & Kahn, C. R. (2005) · Annual Review of Physiology · doi:10.1146/annurev.physiol.68.040104.124723 · Cited by 714
Hyperinsulinemia and risk of Alzheimer disease
Luchsinger, J. A., Tang, M.-X., Shea, S., & Mayeux, R. (2004) · Neurology · doi:10.1212/01.wnl.0000140292.04932.87 · Cited by 683
Role for neuronal insulin resistance in neurodegenerative diseases
Schubert, M., Gautam, D., Surjo, D., Ueki, K., Baudler, S., Schubert, D., Kondo, T., Alber, J., Galldiks, N., Küstermann, E., et al. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308724101 · Cited by 659
Open-channel block of N-methyl-D-aspartate (NMDA) responses by memantine: therapeutic advantage against NMDA receptor-mediated neurotoxicity
Chen, H., Pellegrini, J. W., Aggarwal, S., Lei, S., Warach, S. J., Jensen, F., & Lipton, S. A. (1992) · Journal of Neuroscience · doi:10.1523/jneurosci.12-11-04427.1992 · Cited by 628
Effects of secreted oligomers of amyloid β‐protein on hippocampal synaptic plasticity: a potent role for trimers
Townsend, M., Shankar, G. M., Mehta, T., Walsh, D. M., & Selkoe, D. J. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2005.103754 · Cited by 619
Insulin/IGF-1 and TNF-α stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways
Rui, L., Aguirre, V., Kim, J. K., Shulman, G. I., Lee, A., Corbould, A. M., Dunaif, A. E., & White, M. F. (2001) · Journal of Clinical Investigation · doi:10.1172/jci10934 · Cited by 611
Distinct molecular mechanisms and divergent endocytotic pathways of AMPA receptor internalization
Lin, J., Ju, W. H., Foster, K. A., Lee, S. H., Ahmadian, G., Wyszynski, M. W., Wang, Y. T., & Sheng, M. (2000) · Nature Neuroscience · doi:10.1038/81814 · Cited by 562
Recruitment of functional GABAA receptors to postsynaptic domains by insulin
Wan, Q., Xiong, Z., Man, H., Ackerley, C., Braunton, J., Lu, W. Y., Becker, L. E., MacDonald, J. F., & Wang, Y. T. (1997) · Nature · doi:10.1038/41792 · Cited by 537
Brain Insulin Receptors and Spatial Memory
Zhao, W., Chen, H., Xu, H., Moore, E., Meiri, N., Quon, M. J., & Alkon, D. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.49.34893 · Cited by 532
Soluble oligomers of β amyloid (1-42) inhibit long-term potentiation but not long-term depression in rat dentate gyrus
Wang, H.-W., Pasternak, J. F., Kuo, H., Ristic, H., Lambert, M. P., Chromy, B., Viola, K. L., Klein, W. L., Stine, W. B., Krafft, G. A., et al. (2002) · Brain Research · doi:10.1016/s0006-8993(01)03058-x · Cited by 527
Role of insulin and insulin receptor in learning and memory
Zhao, W., & Alkon, D. L. (2001) · Molecular and Cellular Endocrinology · doi:10.1016/s0303-7207(01)00455-5 · Cited by 498
Activation of Akt/PKB, increased phosphorylation of Akt substrates and loss and altered distribution of Akt and PTEN are features of Alzheimer’s disease pathology
Griffin, R. J., Moloney, A., Kelliher, M., Johnston, J. A., Ravid, R., Dockery, P., O'Connor, R., & O'Neill, C. (2005) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02949.x · Cited by 459
Oligomerization of Alzheimer's β-Amyloid within Processes and Synapses of Cultured Neurons and Brain
Takahashi, R. H., Almeida, C. G., Kearney, P. F., Yu, F., Lin, M. T., Milner, T. A., & Gouras, G. K. (2004) · The Journal of Neuroscience · doi:10.1523/jneurosci.5167-03.2004 · Cited by 445
Alzheimer's disease-type neuronal tau hyperphosphorylation induced by Aβ oligomers
De Felice, F. G., Wu, D., Lambert, M. P., Fernandez, S. J., Velasco, P. T., Lacor, P. N., Bigio, E. H., Jerecic, J., Acton, P. J., Shughrue, P. J., et al. (2008) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2007.02.029 · Cited by 432
Place Learning and Hippocampal Synaptic Plasticity in Streptozotocin-Induced Diabetic Rats
Biessels, G. J., Kamal, A., Ramakers, G. M. J., Urban, I. J. A., Spruijt, B. M., Erkelens, D. W., & Gispen, W. H. (1996) · Diabetes · doi:10.2337/diab.45.9.1259 · Cited by 413
Inflammatory status and insulin resistance
Grimble, R. F. (2002) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/00075197-200209000-00015 · Cited by 411
Beta-amyloid accumulation in APP mutant neurons reduces PSD-95 and GluR1 in synapses
Almeida, C. G., Tampellini, D., Takahashi, R. H., Greengard, P., Lin, M. T., Snyder, E. M., & Gouras, G. K. (2005) · Neurobiology of Disease · doi:10.1016/j.nbd.2005.02.008 · Cited by 397
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
Self-citation
Translocation of PDK-1 to the plasma membrane is important in allowing PDK-1 to activate protein kinase B
Anderson, K. E., Coadwell, J., Stephens, L., & Hawkins, P. T. (1998) · Current Biology · doi:10.1016/s0960-9822(98)70274-x · Cited by 363
Recent Advances in Our Understanding of Insulin Action and Insulin Resistance
Roith, D. L., & Zick, Y. (2001) · Diabetes Care · doi:10.2337/diacare.24.3.588 · Cited by 347
Therapeutic rescue of neurodegeneration in experimental type 3 diabetes: Relevance to Alzheimer's disease
de la Monte, S. M., Tong, M., Lester-Coll, N. H., Plater, M. E., & Wands, J. R. (2006) · Journal of Alzheimer s Disease · doi:10.3233/jad-2006-10113 · Cited by 329
Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice
Pedersen, W. A., McMillan, P. J., Kulstad, J. J., Leverenz, J. B., Craft, S., & Haynatzki, G. R. (2006) · Experimental Neurology · doi:10.1016/j.expneurol.2006.01.018 · Cited by 320
Monoclonal antibodies that target pathological assemblies of Aβ
Lambert, M. P., Velasco, P. T., Chang, L., Viola, K. L., Fernandez, S., Lacor, P. N., Khuon, D., Gong, Y., Bigio, E. H., Shaw, P., et al. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04157.x · Cited by 314
Modulation of memory by insulin and glucose: Neuropsychological observations in Alzheimer’s disease
Watson, G. S., & Craft, S. (2004) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2004.02.048 · Cited by 307
Alzheimer's β-Amyloid Peptides Compete for Insulin Binding to the Insulin Receptor
Xie, L., Helmerhorst, E., Taddei, K., Plewright, B., van Bronswijk, W., & Martins, R. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-10-j0001.2002 · Cited by 291
Therapy insight, type 2 diabetes mellitus and the risk of late-onset Alzheimer's disease
Haan, M. N. (2006) · Nature Clinical Practice Neurology · doi:10.1038/ncpneuro0124 · Cited by 284
Protein kinase B (PKB/Akt) – a key regulator of glucose transport?
Hajduch, É., Litherland, G. J., & Hundal, H. S. (2001) · FEBS Letters · doi:10.1016/s0014-5793(01)02242-6 · Cited by 280
Cognitive effects of insulin in the central nervous system
Park, C. R. (2001) · Neuroscience & Biobehavioral Reviews · doi:10.1016/s0149-7634(01)00016-1 · Cited by 270
Structural differences between insulin receptors in the brain and peripheral target tissues.
Heidenreich, K. A., Zahniser, N. R., Berhanu, P., Brandenburg, D., & Olefsky, J. M. (1983) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)32085-4 · Cited by 265
Role of tyrosine kinase activity in signal transduction by the insulin-like growth factor-I (IGF-I) receptor. Characterization of kinase-deficient IGF-I receptors and the action of an IGF-I-mimetic antibody (alpha IR-3).
Kato, H., Faria, T. N., STANNARD, B. S., Roberts, C. T., & LeRoith, D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53824-2 · Cited by 244
Contribution of cytoskeleton to the internalization of AMPA receptors
Zhou, Q., Xiao, M., & Nicoll, R. A. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.98.3.1261 · Cited by 233
Learning and Memory in Transgenic Mice Modeling Alzheimer's Disease
Ashe, K. H. (2001) · Learning & Memory · doi:10.1101/lm.43701 · Cited by 224
Protein Kinase C-ζ Phosphorylates Insulin Receptor Substrate-1 and Impairs Its Ability to Activate Phosphatidylinositol 3-Kinase in Response to Insulin
Ravichandran, L. V., Esposito, D. L., Chen, J. Y. ‐., & Quon, M. J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m007231200 · Cited by 217
Insulin receptor signaling in long-term memory consolidation following spatial learningPreprint
Dou, J., Chen, M., Dufour, F., Alkon, D. L., & Zhao, W. (2005) · Learning & Memory · doi:10.1101/lm.88005 · Cited by 217
Phosphatidylinositol 3‐kinase is a central mediator of NMDA receptor signalling to MAP kinase (Erk1/2), Akt/PKB and CREB in striatal neurones
Perkinton, M. S., Ip, J. E., Wood, G. L., Crossthwaite, A. J., & Williams, R. J. (2002) · Journal of Neurochemistry · doi:10.1046/j.0022-3042.2001.00699.x · Cited by 212
Effects of hyperglycemia on memory and hormone levels in dementia of the Alzheimer type: A longitudinal study.
Craft, S., Dagogo-Jack, S. E., Wiethop, B. V., Murphy, C., Nevins, R. T., Fleischman, S., Rice, V., Newcomer, J. W., & Cryer, P. E. (1993) · Behavioral Neuroscience · doi:10.1037/0735-7044.107.6.926 · Cited by 191
Akt and PI 3-Kinase Signaling in Cardiomyocyte Hypertrophy and Survival
Matsui, T., Nagoshi, T., & Rosenzweig, A. (2003) · Cell Cycle · doi:10.4161/cc.2.3.381 · Cited by 188
Preparation of Amyloid β‐Protein for Structural and Functional Studies
Teplow, D. B. (2006) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(06)13002-5 · Cited by 187
Akt: Versatile Mediator of Cell Survival and Beyond
Kim, D., & Chung, J. (2002) · BMB Reports · doi:10.5483/bmbrep.2002.35.1.106 · Cited by 184
Solution State Characterization of Amyloid β-Derived Diffusible Ligands
Hepler, R. W., Grimm, K. M., Nahas, D. D., Breese, R., Chen-Dodson, E., Acton, P. J., Keller, P. M., Yeager, M. D., Wang, H., Shughrue, P. J., et al. (2006) · Biochemistry · doi:10.1021/bi061850f · Cited by 182
Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update
Hoyer, S. (2000) · Experimental Gerontology · doi:10.1016/s0531-5565(00)00156-x · Cited by 174
How to build a central synapse: clues from cell culture
Craig, A. M., Graf, E. R., & Linhoff, M. W. (2005) · Trends in Neurosciences · doi:10.1016/j.tins.2005.11.002 · Cited by 170
Insulin Resistance Syndrome and Alzheimer Disease: Pathophysiologic Mechanisms and Therapeutic Implications
Craft, S. (2006) · Alzheimer Disease & Associated Disorders · doi:10.1097/01.wad.0000213866.86934.7e · Cited by 167
Akt activity in Alzheimer’s disease and other neurodegenerative disorders
Rickle, A., Bogdanović, N., Volkmann, I., Winblad, B. G., Ravid, R., & Cowburn, R. F. (2004) · Neuroreport · doi:10.1097/00001756-200404290-00005 · Cited by 166
A Disturbance in the Neuronal Insulin Receptor Signal Transduction in Sporadic Alzheimer's Disease
Frölich, L., Blum-Degen, D., Riederer, P. F., & Hoyer, S. (1999) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.1999.tb07839.x · Cited by 160
Oxidative Stress, Perturbed Calcium Homeostasis, and Immune Dysfunction in Alzheimer's Disease
Mattson, M. P. (2002) · Journal of NeuroVirology · doi:10.1080/13550280290100978 · Cited by 143
Chronic Activation of Protein Kinase C in Soleus Muscles and Other Tissues of Insulin-Resistant Type II diabetic Goto-Kakizaki (GK), Obese/Aged, and Obese/Zucker Rats: A Mechanism For Inhibiting Glycogen Synthesis
Avignon, A., Yamada, K., Zhou, X., Spencer, B. A., Cardona, O., Saba-Siddique, S., Galloway, L. C., Standaert, M. L., & Farese, R. V. (1996) · Diabetes · doi:10.2337/diab.45.10.1396 · Cited by 143
Protein kinase C is increased in the liver of humans and rats with non-insulin-dependent diabetes mellitus: an alteration not due to hyperglycemia.
Considine, R. V., Nyce, M. R., Allen, L. E., Morales, L. M., Triester, S., Serrano, J., Colberg, J., Lanza-Jacoby, S., & Caro, J. F. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118001 · Cited by 141
Akt Mediates the Cross-Talk Between β-Adrenergic and Insulin Receptors in Neonatal Cardiomyocytes
Morisco, C., Condorelli, G., Trimarco, V., Bellis, A., Marrone, C., Condorelli, G., Sadoshima, J., & Trimarco, B. (2005) · Circulation Research · doi:10.1161/01.res.0000152968.71868.c3 · Cited by 141
Enhanced Akt Signaling Is an Early Pro-survival Response That Reflects N-Methyl-D-aspartate Receptor Activation in Huntington's Disease Knock-in Striatal Cells
Ginés, S., Ivanova, E. V., Seong, I., Saura, C. A., & MacDonald, M. E. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m309348200 · Cited by 136
Insulin receptor substrate proteins and diabetes
Lee, Y. H., & White, M. F. (2004) · Archives of Pharmacal Research · doi:10.1007/bf02980074 · Cited by 135
β-Amyloid-induced Dynamin 1 Depletion in Hippocampal Neurons
Kelly, B. L., Vassar, R. J., & Ferreira, A. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m503259200 · Cited by 129
Insulin resistance and non-insulin-dependent diabetes mellitus: cellular and molecular mechanisms
Olefsky, J. M., & Nolan, J. J. (1995) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/61.4.980s · Cited by 124
Mechanism of Insulin Resistance Induced by Sustained Levels of Cytosolic Free Calcium in Rat Adipocytes*
Draznin, B., LEWIS, D., Houlder, N., SHERMAN, N., Adamo, M. L., Garvey, W. T., LeRoith, D., & Sussman, K. E. (1989) · Endocrinology · doi:10.1210/endo-125-5-2341 · Cited by 115
Identification of Enhanced Serine Kinase Activity in Insulin Resistance
Qiao, L. Y., Goldberg, J. L., Russell, J. C., & Sun, X. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.15.10625 · Cited by 111
Synaptic targeting by Aβ oligomers (ADDLS) as a basis for memory loss in early Alzheimer's disease
Klein, W. L. (2006) · Alzheimer s & Dementia · doi:10.1016/j.jalz.2005.11.003 · Cited by 109
Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse model of Alzheimer's disease
PEDERSEN, W., & FLYNN, E. (2004) · Neurobiology of Disease · doi:10.1016/j.nbd.2004.08.003 · Cited by 108
Plasma levels of amyloid β-protein 42 are increased in women with mild cognitive impairment
Assini, A., Cammarata, S., Vitali, A., Colucci, M. E. W., Giliberto, L., Borghi, R., Inglese, M. L., Volpe, S., Ratto, S., Dagna-Bricarelli, F., et al. (2004) · Neurology · doi:10.1212/01.wnl.0000137040.64252.ed · Cited by 104
Unique Features of the Insulin Receptor in Rat Brain
Hendricks, S. A., Agardh, C., Taylor, S. I., & Roth, J. (1984) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1984.tb05387.x · Cited by 95
Diabetes, Alzheimer's disease and apolipoprotein genotype
Messier, C. (2003) · Experimental Gerontology · doi:10.1016/s0531-5565(03)00153-0 · Cited by 92
Protein kinase C isoforms β 1 and β 2 inhibit the tyrosine kinase activity of the insulin receptor
Bossenmaier, B., Mosthaf, L., Mischak, H., Ullrich, A., & Häring, H. (1997) · Diabetologia · doi:10.1007/s001250050761 · Cited by 91
Insulin exerts neuroprotection by counteracting the decrease in cell‐surface GABAA receptors following oxygen–glucose deprivation in cultured cortical neurons
Mielke, J. G., & Wang, Y. T. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02841.x · Cited by 87
Diabetes and brain aging: Epidemiologic evidence
Launer, L. J. (2005) · Current Diabetes Reports · doi:10.1007/s11892-005-0069-1 · Cited by 87
Non‐fibrillar β‐amyloid abates spike‐timing‐dependent synaptic potentiation at excitatory synapses in layer 2/3 of the neocortex by targeting postsynaptic AMPA receptors
Shemer, I., Holmgren, C. D., Min, R., Fülöp, L., Zilberter, M. Y., Sousa, K. M., Farkas, T., Härtig, W., Penke, B., Burnashev, N., et al. (2006) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.2006.04733.x · Cited by 86
Differential effects of IRS1 phosphorylated on Ser307 or Ser632 in the induction of insulin resistance by oxidative stress
Bloch-Damti, A., Potashnik, R., Gual, P., MARCHAND‐BRUSTEL, Y. L., Tanti, J., Rudich, A., & Bashan, N. (2006) · Diabetologia · doi:10.1007/s00125-006-0349-6 · Cited by 85
Alterations in Glucose Metabolism in Patients with Alzheimer's Disease
Meneilly, G. S., & Hill, A. (1993) · Journal of the American Geriatrics Society · doi:10.1111/j.1532-5415.1993.tb07458.x · Cited by 79
Insulin Receptors from Guinea Pig Liver and Brain:Structural and Functional Studies
Lowe, W. L., & LeRoith, D. (1986) · Endocrinology · doi:10.1210/endo-118-4-1669 · Cited by 45
PGH2‐derived levuglandin adducts increase the neurotoxicity of amyloid β1–42
Boutaud, O. G., Montine, T. J., Chang, L., Klein, W. L., & Oates, J. A. (2006) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2005.03586.x · Cited by 44
Chronic activation of protein kinase C in soleus muscles and other tissues of insulin-resistant type II diabetic Goto-Kakizaki (GK), obese/aged, and obese/Zucker rats. A mechanism for inhibiting glycogen synthesis
Avignon, A., Yamada, K., Zhou, X., et al. (1996) · Diabetes · doi:10.2337/diabetes.45.10.1396 · Cited by 37
Amyloid β protein activates PKC-δ and induces translocation of myristoylated alanine-rich C kinase substrate (MARCKS) in microglia
Nakai, M., Tanimukai, S., Yagi, K., Saito, N., Taniguchi, T., Terashima, A., Kawamata, T., Yamamoto, H., Fukunaga, K., Miyamoto, E., et al. (2001) · Neurochemistry International · doi:10.1016/s0197-0186(00)00126-1 · Cited by 36
Another Role for the Celebrity
Tian, R. (2005) · Circulation Research · doi:10.1161/01.res.0000156076.17807.1f · Cited by 35
Deregulation of the Phosphatidylinositol-3 Kinase Signaling Cascade Is Associated with Neurodegeneration in Npc1−/− Mouse Brain
Bi, X., Liu, J., Yao, Y., Baudry, M., & LYNCH, G. S. (2005) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)61197-2 · Cited by 32
Specific localization of the annexin II heterotetramer in brain lipid raft fractions and its changes in spatial learning
Zhao, W., Waisman, D. M., & GRIMALDI, M. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02509.x · Cited by 32
Postbinding characterization of five naturally occurring mutations in the human insulin receptor gene: impaired insulin-stimulated c-jun expression and thymidine incorporation despite normal receptor autophosphorylation
Quon, M. J., Cama, A., & Taylor, S. I. (1992) · Biochemistry · doi:10.1021/bi00156a013 · Cited by 25
Molecules that Disrupt Memory Circuits in Alzheimer’s Disease: The Attack on Synapses by Aβ Oligomers (ADDLs)
Klein, W. L., Lacor, P. N., Felice, F. G. D., & Ferreira, S. T. (2007) · Research and perspectives in neurosciences · doi:10.1007/978-3-540-45702-2_11 · Cited by 23
Specific Binding of Insulin to Membranes from Dendrodendritic Synaptosomes of Rat Olfactory Bulb
Matsumoto, H., & Rhoads, D. E. (1990) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1990.tb13321.x · Cited by 23
Modulation of Insulin Receptor Signaling: Potential Mechanisms of a Cross Talk Between Bradykinin and the Insulin Receptor
Häring, H., Tippmer, S., Kellerer, M., Mosthaf, L., Kroder, G., Bossenmaier, B., & Berti, L. (1996) · Diabetes · doi:10.2337/diab.45.1.s115 · Cited by 23
Plasma levels of insulin and amyloid β42 are correlated in patients with amnestic Mild Cognitive Impairment
Odetti, P. R., Piccini, A., Giliberto, L., Borghi, R., Natale, A., Monacelli, F., Marchese, M., Assini, A., Colucci, M., Cammarata, S., et al. (2005) · Journal of Alzheimer s Disease · doi:10.3233/jad-2005-8303 · Cited by 19
Different cellular localization, translocation, and insulin‐induced phosphorylation of PKBα in HepG2 cells and hepatocytes
Syed, N., Horner, K. N., Misra, V., & Khandelwal, R. L. (2002) · Journal of Cellular Biochemistry · doi:10.1002/jcb.10189 · Cited by 17
TPA inhibits insulin stimulated PIP hydrolysis in fat cell membranes: Evidence for modulation of insulin dependent phospholipase C by proteinkinase C
Kellerer, M., Seffer, E., Mushack, J., Obermaier-Kusser, B., & Häring, H. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90693-h · Cited by 16
Genetic determinants of type 2 diabetes mellitus: lessons learned from family studies.
Froguel, P., Velho, G., Passa, P., & Cohen, D. (1993) · PubMed · Cited by 14
Nanomolar amyloid β protein activates a specific PKC isoform mediating phosphorylation of MARCKS in Neuro2A cells
Tanimukai, S., Hasegawa, H., Nakai, M., Yagi, K., Hirai, M., Saito, N., Taniguchi, T., Terashima, A., Yasuda, M., Kawamata, T., et al. (2002) · Neuroreport · doi:10.1097/00001756-200203250-00037 · Cited by 9
Peptide mapping on Northern blot analyses of insulin receptors in brain and adipocytes
Heidenreich, K. A., Gilmore, P. R., Brandenburg, D., & Hatada, E. N. (1988) · Molecular and Cellular Endocrinology · doi:10.1016/0303-7207(88)90068-8 · Cited by 8
Insulin, diabetes mellitus, Alzheimer's disease, and apolipoprotein E
Gambassi, G., & Bernabei, R. (1998) · Neurology · doi:10.1212/wnl.51.3.925-b · Cited by 4

Research works printed but not linked: 8

Abramoff M. D., 2004, Image processing with Image, J. Biophotonics Int., 11, 36
10.1161/01.RES.0000152968.71868.c3 · DOI
Stevens G. R.(1998)Signaling proteins in Alzheimer's Disease: The possible roles of focal adhesion kinase paxillin and protein kinase C. Ph.D. thesis pp.101–112 Northwestern University
10.1007/s001250050761 · DOI
Stevens G. R.(1998)Signaling proteins in Alzheimer's Disease: the possible roles of focal adhesion kinase paxillin and protein kinase C. Ph.D. thesis pp101–112 Northwestern University
10.1161/01.RES.0000152968.71868.c3 · DOI
10.1007/BF02980074 · DOI
10.1038/41792 · DOI

Sorted by citations

Demonstrated brain insulin resistance in Alzheimer’s disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline
Talbot, K., Wang, H.-Y., Kazi, H., Han, L.-Y., Bakshi, K. P., Stucky, A., Fuino, R. L., Kawaguchi, K. R., Samoyedny, A. J., Wilson, R. S., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59903 · Cited by 1,871
The Amyloid-β Oligomer Hypothesis: Beginning of the Third Decade
Cline, E. N., Bicca, M. A., Viola, K. L., & Klein, W. L. (2018) · Journal of Alzheimer's Disease · doi:10.3233/jad-179941 · Cited by 870
Self-citation
An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer’s disease–associated Aβ oligomers
Bomfim, T. R., Forny‐Germano, L., Sathler, L. B., Brito‐Moreira, J., Houzel, J., Decker, H., Silverman, M. A., Kazi, H., Melo, H. M., McClean, P. L., et al. (2012) · Journal of Clinical Investigation · doi:10.1172/jci57256 · Cited by 849
Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer’s disease indicate possible resistance to IGF-1 and insulin signalling
Moloney, A. M., Griffin, R. J., Timmons, S., O’Connor, R., Ravid, R., & O’Neill, C. (2010) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2008.04.002 · Cited by 764
Decoding Alzheimer's disease from perturbed cerebral glucose metabolism: Implications for diagnostic and therapeutic strategies
Chen, Z., & Zhong, C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.004 · Cited by 698

See all 590

Authors: Zhao, W., De Felice, F. G., Fernandez, S., Chen, H., Lambert, M. P., Quon, M. J., Krafft, G. A., & Klein, W. L.
Affiliations: Department of Neurobiology and Physiology Northwestern University Evanston Illinois USA
Northwestern University (US)
National Institutes of Health (US)
Blanchette Rockefeller Neurosciences Institute (US)
Acumen Pharmaceuticals (United States) (US)
ORCID: Quon, Michael J.
Klein, William L.
Venue: The FASEB Journal
Publisher: Wiley
Published: 2007-08-24
Volume: 22
Issue: 1
Pages: 246-260
ISSN: 0892-6638 (ISSN-L)
1530-6860
DOI: 10.1096/fj.06-7703com
OpenAlex: W2144486959
Semantic Scholar: 0a3dc4e52b02b85d3d180f43a62aee9078ca629b
Cited by: 587
References: 109
Citations by year: 2026: 13 · 2025: 21 · 2024: 21 · 2023: 22 · 2022: 37 · 2021: 34 · 2020: 28 · 2019: 29 · 2018: 38 · 2017: 42 · 2016: 51 · 2015: 46 · 2014: 35 · 2013: 30 · 2012: 39
FWCI: 14.69
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: The FASEB Journal (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Aging (RO1‐AG18877)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords: amyloid-beta oligomers, Alzheimer's disease, insulin resistance, insulin signaling, tyrosine autophosphorylation, NMDA receptor, Akt phosphorylation, hippocampal neurons, synaptic dysfunction
MeSH terms: Animals, Biopolymers, Cells, Cultured, Dendrites, Humans, Insulin, Neurons, Phosphorylation, Protein-Tyrosine Kinases, Receptor, Insulin, Signal Transduction, Receptors, N-Methyl-D-Aspartate, Amyloid beta-Peptides, Rats, Sprague-Dawley, 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

Amyloid beta oligomers induce impairment of neuronal insulin receptors

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks