Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease
Abstract
Advanced glycation end products (AGE) and the receptor for AGE (RAGE) have been implicated in the chronic complications of diabetes mellitus (DM), and have been reported to play an important role in the pathogenesis of Alzheimer's disease (AD). In this study, we established a polyclonal anti-RAGE antibody, and examined the immunohistochemical localization of amyloid beta protein (Abeta), AGE, and RAGE in neurons and astrocytes from patients with AD and DM. Our anti-RAGE antibody recognized full-length RAGE (50 kd) and N-terminal RAGE (35 kd) in human brain tissue. Abeta-, AGE-, and RAGE-positive granules were identified in the perikaryon of hippocampal neurons (especially from CA3 and CA4) in all subjects. The distribution and staining pattern of these immunopositive granules showed good concordance with each antibody. In AD, most astrocytes contained both AGE-and RAGE-positive granules and their distribution was almost the same. Abeta-positive granules were less common, but Abeta-, AGE-, and RAGE-positive granules were colocalized in one part of a single astrocyte. In DM patients and control cases, AGE-and RAGE-positive astrocytes were very rare. These finding support the hypothesis that glycated Abeta is taken up via RAGE and is degraded through the lysosomal pathway in astrocytes. In addition to the presence of AGE, the process of AGE degradation and receptor-mediated reactions may contribute to neuronal dysfunction and promote the progression of AD.
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RAGE receptors are overexpressed in the BBB and astrocytes, especially in brain tissue from AD animal models and AD patients.
“Our previous research and that of others found that RAGE receptors are overexpressed in the BBB and astrocytes, especially in brain tissue from AD animal models and AD patients.33–35”
From Reverse the progression of Alzheimer’s disease through Nano-ERASER-based adult neuroregeneration (2026) · cites this paper as [34]
Higher levels of RAGE expression are found in neuronal, microglial, and endothelial cells in Alzheimer's disease patients compared with age-matched non-demented controls.
“AGEs and the receptor for advanced glycation end-products (RAGE) can play an important role in AD pathogenesis as higher levels of RAGE expression in neuronal, microglial, and endothelial cells in patients with AD compared with age-matched, non- demented controls are found [43,44,45,46].”
From Role of Oxidative Damage in Alzheimer’s Disease and Neurodegeneration: From Pathogenic Mechanisms to Biomarker Discovery (2021) · cites this paper as [46]
Cites
Towbin, H., Staehelin, T., & Gordon, J. (1979) · Proceedings of the National Academy of Sciences of the United States of America · doi:10.1073/pnas.76.9.4350 · Cited by 51,421 · see citing works
RAGE and amyloid-β peptide neurotoxicity in Alzheimer's disease
Yan, S. D., Chen, X., Fu, J., Chen, M., Zhu, H., Roher, A., Slattery, T., Zhao, L., Nagashima, M., Morser, J., et al. (1996) · Nature · doi:10.1038/382685a0 · Cited by 2,012 · see citing works
Neeper, M. P., Schmidt, A. M., Brett, J., Yan, S. D., Wang, F., Pan, Y., Elliston, K. O., Stern, D., & SHAW, A. R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42138-2 · Cited by 1,542 · see citing works
Nonenzymatic Glycosylation and the Pathogenesis of Diabetic Complications
Brownlee, M., Vlassara, H., & Cerami, A. (1984) · Annals of Internal Medicine · doi:10.7326/0003-4819-101-4-527 · Cited by 1,017 · see citing works
Vlassara, H., Bucala, R., & Striker, L. J. (1994) · PubMed · Cited by 851 · see citing works
Brett, J., Schmidt, A. M., Yan, S. D., Zou, Y. S., Weidman, E., Pinsky, D. J., Nowygrod, R., Neeper, M. P., Przysiecki, C. T., & SHAW, A. R. (1993) · PubMed Central · Cited by 776 · see citing works
Nonenzymatic Browning in Vivo: Possible Process for Aging of Long-Lived Proteins
Monnier, V. M., & Cerami, A. (1981) · Science · doi:10.1126/science.6779377 · Cited by 768 · see citing works
The Pathogenesis of Senile Plaques
DICKSON, D. W. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199704000-00001 · Cited by 753 · see citing works
New Aspects of the Maillard Reaction in Foods and in the Human Body
Ledl, F., & Schleicher, E. D. (1990) · Angewandte Chemie International Edition in English · doi:10.1002/anie.199005653 · Cited by 738 · see citing works
Advanced Maillard reaction end products are associated with Alzheimer disease pathology.
Smith, M. A., Taneda, S., Richey, P. L., Miyata, S., Yan, S. D., Stern, D., Sayre, L. M., Monnier, V. M., & Perry, G. L. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.12.5710 · Cited by 715 · see citing works
Immunochemical detection of advanced glycosylation end products in vivo.
Makita, Z., Vlassara, H., Cerami, A., & Bucala, R. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)42741-x · Cited by 491 · see citing works
Self-citationAdvanced Glycation End Products in Alzheimer's Disease and Other Neurodegenerative Diseases
Sasaki, N., Fukatsu, R., Tsuzuki, K., Hayashi, Y., Yoshida, T., Fujii, N., Koike, T., WAKAYAMA, I., Yanagihara, R. T., Garruto, R. M., et al. (1998) · American Journal Of Pathology · doi:10.1016/s0002-9440(10)65659-3 · Cited by 409 · see citing works
Self-citationAstrocytes Regulate Microglial Phagocytosis of Senile Plaque Cores of Alzheimer's Disease
DeWitt, D. A., Perry, G., Cohen, M., Doller, C., & Silver, J. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6738 · Cited by 261 · see citing works
Hemoglobin-AGE: A Circulating Marker of Advanced Glycosylation
Makita, Z., Vlassara, H., Rayfield, E. J., Cartwright, K. J., Friedman, E. A., Rodby, R. A., Cerami, A., & Bucala, R. (1992) · Science · doi:10.1126/science.1411574 · Cited by 251 · see citing works
Self-citationAraki, N., Higashi, T., Mori, T., Shibayama, R., Kawabe, Y., Kodama, T., Takahashi, K., Shichiri, M., & Horiuchi, S. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.0408h.x · Cited by 248 · see citing works
Yang, Z., Makita, Z., Horii, Y., Brunelle, S., Cerami, A., Sehajpal, P. K., Suthanthiran, M., & Vlassara, H. (1991) · The Journal of Experimental Medicine · doi:10.1084/jem.174.3.515 · Cited by 191 · see citing works
Self-citationDiabetics do not have increased Alzheimer-type pathology compared with age-matched control subjects
Heitner, J., & Dickson, D. (1997) · Neurology · doi:10.1212/wnl.49.5.1306 · Cited by 173 · see citing works
(1998) · Europe PMC (PubMed Central) · Cited by 146 · see citing works
Synergistic Induction of Nitric Oxide by β-Amyloid and Cytokines in Astrocytes
Rossi, F., & Bianchini, E. (1996) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1996.1197 · Cited by 134 · see citing works
Yamaguchi, H., Sugihara, S., Ogawa, A., Saido, T. C., & Ihara, Y. (1998) · Acta Neuropathologica · doi:10.1007/s004010050790 · Cited by 110 · see citing works
Akiyama, H., Schwab, C., Kondo, H., Mori, H., Kametani, F., Ikeda, K., & McGeer, P. L. (1996) · Neuroscience Letters · doi:10.1016/s0304-3940(96)12474-5 · Cited by 76 · see citing works
Yan, S. D., Stern, D., & Schmidt, A. M. (1997) · European Journal of Clinical Investigation · doi:10.1046/j.1365-2362.1996.00072.x · Cited by 74 · see citing works
Takeda, A., Yasuda, T., Miyata, T., Goto, Y., Wakai, M., Watanabe, M., Yasuda, Y., Horie, K., Inagaki, T., Doyu, M., et al. (1998) · Acta Neuropathologica · doi:10.1007/s004010050839 · Cited by 71 · see citing works
Age-dependent accumulation of advanced glycosylation end products in human neurons
Li, J., Surini, M., Catsicas, S., Kawashima, E. H., & Bouras, C. (1995) · Neurobiology of Aging · doi:10.1016/0197-4580(95)80009-g · Cited by 66 · see citing works
Nishino, T., Horii, Y., Shiiki, H., Yamamoto, H., Makita, Z., Bucala, R., & Dohi, K. (1995) · Human Pathology · doi:10.1016/0046-8177(95)90063-2 · Cited by 62 · see citing works
Self-citationReceptors for Advanced Glycosylation Endproducts in Human Brain: Role in Brain Homeostasis
Li, J., Dickson, D. W., Hof, P. R., & Vlassara, H. (1998) · Molecular Medicine · doi:10.1007/bf03401729 · Cited by 61 · see citing works
Schmidpeter, A., & Ebeling, J. (1967) · Angewandte Chemie International Edition in English · doi:10.1002/anie.196705651 · Cited by 34 · see citing works
Is amyloid β-protein glycated in Alzheimerʼs disease?
Tabaton, M., Perry, G. L., Smith, M. A., Vitek, M. P., Angelini, G., Dapino, D., Garibaldi, S., Zaccheo, D., & Odetti, P. R. (1997) · Neuroreport · doi:10.1097/00001756-199703030-00018 · Cited by 20 · see citing works
'Toxicity of glucose: is AGE the answer?'
Makita, Z. (1995) · Nephrology Dialysis Transplantation · doi:10.1093/ndt/10.supp7.33 · Cited by 15 · see citing works
Self-citation
Flagged first, then by citations
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Sorted by citations
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 · see citing works
Astrocytes are active players in cerebral innate immunity
Farina, C., Aloisi, F., & Meinl, E. (2007) · Trends in Immunology · doi:10.1016/j.it.2007.01.005 · Cited by 1,304 · see citing works
Increased Risk of Type 2 Diabetes in Alzheimer Disease
Janson, J., Laedtke, T., Parisi, J. E., O’Brien, P., Petersen, R. C., & Butler, P. C. (2004) · Diabetes · doi:10.2337/diabetes.53.2.474 · Cited by 950 · see citing works
Cognitive Dysfunction and Diabetes Mellitus
Kodl, C. T., & Seaquist, E. R. (2008) · Endocrine Reviews · doi:10.1210/er.2007-0034 · Cited by 823 · see citing works
Common neurodegenerative pathways in obesity, diabetes, and Alzheimer's disease
Pugazhenthi, S., Qin, L., & Reddy, P. H. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.04.017 · Cited by 697 · see citing works
Chen, Z., & Zhong, C. (2013) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2013.06.004 · Cited by 671 · see citing works
RAGE, LRP-1, and amyloid-beta protein in Alzheimer’s disease
Donahue, J. E., Flaherty, S. L., Johanson, C. E., Duncan, J. A., Silverberg, G. D., Miller, M. C., Tavares, R., Yang, W., Wu, Q., Sabo, E., et al. (2006) · Acta Neuropathologica · doi:10.1007/s00401-006-0115-3 · Cited by 519 · see citing works
How does diabetes accelerate Alzheimer disease pathology?
Sims-Robinson, C., Kim, B., Rosko, A., & Feldman, E. L. (2010) · Nature Reviews Neurology · doi:10.1038/nrneurol.2010.130 · Cited by 492 · see citing works
Morphologic Findings of Coronary Atherosclerotic Plaques in Diabetics
BURKE, A. P., Kolodgie, F. D., Zieske, A. W., Fowler, D. R., Weber, D. K., Varghese, P. J., Farb, A. A., & Virmani, R. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000131783.74034.97 · Cited by 490 · see citing works
Taniguchi, N., Kawahara, K.-I., Yone, K., Hashiguchi, T., Yamakuchi, M., Goto, M., Inoue, K., Yamada, S., Ijiri, K., Matsunaga, S., et al. (2003) · Arthritis & Rheumatism · doi:10.1002/art.10859 · Cited by 482 · see citing works
Receptor for Advanced Glycation End-Products is a Marker of Type I Cell Injury in Acute Lung Injury
Uchida, T., Shirasawa, M., Ware, L. B., 小島, 勝., Hata, Y., Makita, K., Mednick, G., Matthay, Z. A., & Matthay, M. A. (2006) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.200509-1477oc · Cited by 468 · see citing works
RAGE regulation and signaling in inflammation and beyond
Kierdorf, K., & Fritz, G. (2013) · Journal of Leukocyte Biology · doi:10.1189/jlb.1012519 · Cited by 434 · see citing works
Molecular Mechanisms of Amyloid Oligomers Toxicity
Kayed, R., & Lasagna‐Reeves, C. A. (2012) · Journal of Alzheimer s Disease · doi:10.3233/jad-2012-129001 · Cited by 417 · see citing works
Common pathological processes in Alzheimer disease and type 2 diabetes: A review
Li, L., & Hölscher, C. (2007) · Brain Research Reviews · doi:10.1016/j.brainresrev.2007.09.001 · Cited by 367 · see citing works
Fang, F., Lue, L.-F., Yan, S., Xu, H., Luddy, J. S., Chen, D., Walker, D. G., Stern, D. M., Yan, S., Schmidt, A. M., et al. (2010) · The FASEB Journal · doi:10.1096/fj.09-139634 · Cited by 335 · see citing works
Targeting the Receptor for Advanced Glycation Endproducts (RAGE): A Medicinal Chemistry Perspective
Bongarzone, S., Savickas, V., Luzi, F., & Gee, A. D. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00058 · Cited by 313 · see citing works
Glial protein S100B modulates long-term neuronal synaptic plasticity
Nishiyama, H., Knöpfel, T., Endo, S., & Itohara, S. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.052020999 · Cited by 288 · see citing works
Li, L., Acioglu, C., Heary, R. F., & Elkabes, S. (2021) · Brain, Behavior, and Immunity · doi:10.1016/j.bbi.2020.10.007 · Cited by 283 · see citing works
Proteins in Human Brain Cortex Are Modified by Oxidation, Glycoxidation, and Lipoxidation
Pamplona, R., Dalfó, E., Ayala, V., Bellmunt, M. J., Prat, J., Ferrer, I., & Portero‐Otín, M. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502255200 · Cited by 280 · see citing works
Paudel, Y. N., Angelopoulou, E., Piperi, C., Othman, I., Aamir, K., & Shaikh, M. F. (2020) · Cells · doi:10.3390/cells9020383 · Cited by 257 · see citing works
Leclerc, E., Fritz, G., Weibel, M., Heizmann, C. W., & Galichet, A. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m703951200 · Cited by 264 · see citing works
Verdier, Y., Zarándi, M., & Penke, B. (2004) · Journal of Peptide Science · doi:10.1002/psc.573 · Cited by 261 · see citing works
Diabetes and Alzheimer’s disease crosstalk
Baglietto‐Vargas, D., Shi, J. J., Yaeger, D. M., Ager, R. R., & LaFerla, F. M. (2016) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2016.03.005 · Cited by 254 · see citing works
Valente, T., Gella, A., Fernàndez‐Busquets, X., Unzeta, M., & Durany, N. (2009) · Neurobiology of Disease · doi:10.1016/j.nbd.2009.09.008 · Cited by 210 · see citing works
AGEs induce Alzheimer-like tau pathology and memory deficit via RAGE-mediated GSK-3 activation
Li, X., Lv, B.-L., Xie, J., Liu, J., Zhou, X., & Wang, J. (2011) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2011.02.003 · Cited by 207 · see citing works
Activation of toll-like receptor, RAGE and HMGB1 signalling in malformations of cortical development
Zurolo, E., Iyer, A., Maroso, M., Carbonell, C., Anink, J. J., Ravizza, T., Fluiter, K., Spliet, W. G. M., van Rijen, P. C., Vezzani, A., et al. (2011) · Brain · doi:10.1093/brain/awr032 · Cited by 184 · see citing works
Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue
Casula, M., Iyer, A. M., Spliet, W. G. M., Anink, J. J., Steentjes, K., Sta, M., Troost, D., & Aronica, E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.02.001 · Cited by 200 · see citing works
Hippocampal RAGE immunoreactivity in early and advanced Alzheimer’s disease
Miller, M. C., Tavares, R., Johanson, C. E., Hovanesian, V., Donahue, J. E., Gonzalez, L., Silverberg, G. D., & Stopa, E. G. (2008) · Brain Research · doi:10.1016/j.brainres.2008.06.124 · Cited by 194 · see citing works
Carbonyl Toxicology and Alzheimer's Disease
Picklo, M. J. (2002) · Toxicology and Applied Pharmacology · doi:10.1006/taap.2002.9506 · Cited by 194 · see citing works
Rojas-Gutierrez, E., Muñoz‐Arenas, G., Treviño, S., Espinosa, B., Chávez, R., Rojas, K., Flores, G., Díaz, A., & Guevara, J. (2017) · Synapse · doi:10.1002/syn.21990 · Cited by 193 · see citing works
Lüth, H. J. (2004) · Cerebral Cortex · doi:10.1093/cercor/bhh123 · Cited by 186 · see citing works
Accelerated diabetic glomerulopathy in galectin‐3/AGE receptor 3 knockout mice
Pugliese, G., Pricci, F., Iacobini, C., Leto, G., Amadio, L., Barsotti, P., Frigeri, L. G., Hsu, D. K., Vlassara, H., Liu, F., et al. (2001) · The FASEB Journal · doi:10.1096/fj.01-0006com · Cited by 184 · see citing works
Chornenkyy, Y., Wang, W., Wei, A. L., & Nelson, P. T. (2018) · Brain Pathology · doi:10.1111/bpa.12655 · Cited by 184 · see citing works
Buccellato, F. R., D’Anca, M., Fenoglio, C., Scarpini, E., & Galimberti, D. (2021) · Antioxidants · doi:10.3390/antiox10091353 · Cited by 179 · see citing works
Human cerebral neuropathology of Type 2 diabetes mellitus
Nelson, P. T., Smith, C. D., Abner, E. L., Schmitt, F. A., Scheff, S. W., Davis, G. J., Keller, J. N., Jicha, G. A., Davis, D. G., Wang, W., et al. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.08.005 · Cited by 177 · see citing works
Glycation exacerbates the neuronal toxicity of β-amyloid
Li, X.-H., Du, L.-L., Cheng, X.-S., Jiang, X., Zhang, Y., Lv, B.-L., Liu, R., Wang, J.-Z., & Zhou, X.-W. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.180 · Cited by 178 · see citing works
Advanced glycation end-products (AGEs): involvement in aging and in neurodegenerative diseases
GRILLO, M. A., & Colombatto, S. (2007) · Amino Acids · doi:10.1007/s00726-007-0606-0 · Cited by 177 · see citing works
Glycation—a sweet tempter for neuronal death
Kikuchi, S. (2003) · Brain Research Reviews · doi:10.1016/s0165-0173(02)00273-4 · Cited by 169 · see citing works
The sour side of neurodegenerative disorders: the effects of protein glycation
Miranda, H. V., & Outeiro, T. F. (2009) · The Journal of Pathology · doi:10.1002/path.2682 · Cited by 168 · see citing works
Salahuddin, P., Rabbani, G., & Khan, R. H. (2014) · Cellular & Molecular Biology Letters · doi:10.2478/s11658-014-0205-5 · Cited by 167 · see citing works
Inflammatory S100A9 and S100A12 proteins in Alzheimer's disease
Shepherd, C. E., Goyette, J., Utter, V., Rahimi, F., Yang, Z., Geczy, C. L., & Halliday, G. M. (2006) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2005.09.033 · Cited by 161 · see citing works
Iori, V., Maroso, M., Rizzi, M., Iyer, A. M., Vertemara, R., Carli, M., Agresti, A., Antonelli, A., Bianchi, M. E., Aronica, E., et al. (2013) · Neurobiology of Disease · doi:10.1016/j.nbd.2013.03.006 · Cited by 159 · see citing works
Ebrahimpour, S., Zakeri, M., & Esmaeili, A. (2020) · Ageing Research Reviews · doi:10.1016/j.arr.2020.101095 · Cited by 158 · see citing works
Tezel, G., Luo, C., & Yang, X. (2007) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.06-0737 · Cited by 155 · see citing works
Expression analysis of S100 proteins and RAGE in human tumors using tissue microarrays
Hsieh, H.-L., Schäfer, B. W., Sasaki, N., & Heizmann, C. W. (2003) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(03)01190-2 · Cited by 151 · see citing works
Self-citationNeuroinflammation and anti-inflammatory therapy for Alzheimer’s disease
Moore, A. H., & O’Banion, M. K. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00162-x · Cited by 146 · see citing works
Regulation of Human Melanoma Growth and Metastasis by AGE–AGE Receptor Interactions
Abe, R., Shimizu, T., Sugawara, H., Watanabe, H., Nakamura, H., Choei, H., Sasaki, N., Yamagishi, S., Shimizu, H., & Takeuchi, M. (2004) · Journal of Investigative Dermatology · doi:10.1046/j.0022-202x.2004.22218.x · Cited by 145 · see citing works
Self-citationWu, L., Ahmadvand, D., Su, J., Hall, A., Tan, X., Farhangrazi, Z. S., & Moghimi, S. M. (2019) · Nature Communications · doi:10.1038/s41467-019-12554-2 · Cited by 140 · see citing works
Park, I. H. (2004) · Molecular Immunology · doi:10.1016/j.molimm.2003.11.027 · Cited by 140 · see citing works
RAGE: A Multi-Ligand Receptor Unveiling Novel Insights in Health and Disease
Alexiou, P., Chatzopoulou, M., Pegklidou, K., & Demopoulos, V. J. (2010) · Current Medicinal Chemistry · doi:10.2174/092986710791331086 · Cited by 138 · see citing works
Physical Exercise Enhances Neuroplasticity and Delays Alzheimer’s Disease
Lin, T.-W., Tsai, S., & Kuo, Y. (2018) · Brain Plasticity · doi:10.3233/bpl-180073 · Cited by 146 · see citing works
Site-Specific Blockade of RAGE-V<sub>d</sub>Prevents Amyloid-β Oligomer Neurotoxicity
Sturchler, E., Galichet, A., Weibel, M., Leclerc, E., & Heizmann, C. W. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.4878-07.2008 · Cited by 136 · see citing works
Little, K., Llorián‐Salvador, M., Scullion, S., Hernández, C., Simó‐Servat, O., del Marco, À., Bosma, E. K., Vargas-Soria, M., Carranza-Naval, M. J., Bergen, T. V., et al. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.10.008 · Cited by 136 · see citing works
Toxic Advanced Glycation End Products (TAGE) Theory in Alzheimer’s Disease
Sato, T., Shimogaito, N., Wu, X., Kikuchi, S., Yamagishi, S., & Takeuchi, M. (2006) · American Journal of Alzheimer s Disease & Other Dementias® · doi:10.1177/1533317506289277 · Cited by 133 · see citing works
Self-citationMechanism of glial activation by S100B: involvement of the transcription factor NFκB
Lam, A. G. M., Koppal, T., Akama, K. T., Guo, L., Craft, J. M., Samy, B., Schavocky, J. P., Watterson, D. M., & Eldik, L. J. V. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00233-0 · Cited by 126 · see citing works
Takeuchi, M., & Yamagishi, S. (2009) · Journal of Alzheimer s Disease · doi:10.3233/jad-2009-0974 · Cited by 122 · see citing works
Self-citationHamilton, A., & Hölscher, C. (2012) · Brain Research · doi:10.1016/j.brainres.2012.02.015 · Cited by 121 · see citing works
Current therapeutic targets for the treatment of Alzheimer’s disease
Grill, J. D., & Cummings, J. L. (2010) · Expert Review of Neurotherapeutics · doi:10.1586/ern.10.29 · Cited by 121 · see citing works
Accumulation of intraneuronal Aβ correlates with ApoE4 genotype
Christensen, D. Z., Schneider-Axmann, T., Lucassen, P. J., Bayer, T. A., & Wirths, O. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0666-1 · Cited by 120 · see citing works
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Monterey, M. D., Wei, H., Wu, X., & Wu, J. Q. (2021) · Frontiers in Neurology · doi:10.3389/fneur.2021.619626 · Cited by 117 · see citing works
TAGE (toxic AGEs) hypothesis in various chronic diseases
Takeuchi, M., & Yamagishi, S. (2004) · Medical Hypotheses · doi:10.1016/j.mehy.2004.02.042 · Cited by 116 · see citing works
Self-citationd-ribose in glycation and protein aggregation
Yan, W., Han, C. S., Zhou, J., Liu, Y. M., Chen, L., & He, R. Q. (2012) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2012.01.005 · Cited by 113 · see citing works
RAGE-TLR Crosstalk Sustains Chronic Inflammation in Neurodegeneration
Gąsiorowski, K., Brokos, B., Echeverrı́a, V., Barreto, G. E., & Leszek, J. (2017) · Molecular Neurobiology · doi:10.1007/s12035-017-0419-4 · Cited by 117 · see citing works
Mruthinti, S., Buccafusco, J. J., Hill, W., Waller, J. L., Jackson, T. W., ZAMRINI, E. Y., & Schade, R. (2004) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2003.11.001 · Cited by 113 · see citing works
Choi, B.-R., Cho, W.-H., Kim, J., Lee, H. J., Chung, C., Jeon, W. K., & Han, J.-S. (2014) · Experimental & Molecular Medicine · doi:10.1038/emm.2013.147 · Cited by 111 · see citing works
Silverberg, G. D., Miller, M. C., Messier, A. A., Majmudar, S., Machan, J. T., Donahue, J. E., Stopa, E. G., & Johanson, C. E. (2009) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/nen.0b013e3181c8ad2f · Cited by 110 · see citing works
Oligomer-specific Aβ toxicity in cell models is mediated by selective uptake
Chafekar, S. M., Baas, F., & Scheper, W. (2008) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2008.06.003 · Cited by 110 · see citing works
Sasaki, N., Takeuchi, M., Chowei, H., Kikuchi, S., Hayashi, Y., Nakano, N., Ikeda, H., Yamagishi, S., Kitamoto, T., Saito, T., et al. (2002) · Neuroscience Letters · doi:10.1016/s0304-3940(02)00310-5 · Cited by 105 · see citing works
Self-citationFang, F., Yu, Q., Arancio, O., Chen, D., Gore, S. S., Yan, S. S., & Yan, S. F. (2018) · Human Molecular Genetics · doi:10.1093/hmg/ddy017 · Cited by 103 · see citing works
Heterogeneity Affecting Outcome From Acute Stroke Therapy
Kent, T. A., Soukup, V. M., & Fabian, R. H. (2001) · Stroke · doi:10.1161/hs1001.096588 · Cited by 103 · see citing works
Hsieh, H., Schäfer, B. W., Weigle, B., & Heizmann, C. W. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.02.135 · Cited by 103 · see citing works
Involvement of maillard reactions in Alzheimer disease
Reddy, V. P., Obrenovich, M. E., Atwood, C., Perry, G. L., & Smith, M. A. (2002) · Neurotoxicity Research · doi:10.1080/1029840290007321 · Cited by 101 · see citing works
Ko, S., Lin, Y.-P., Lin, Y.-S., & Chang, S.-S. (2010) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2010.05.005 · Cited by 99 · see citing works
Role of amyloid peptides in vascular dysfunction and platelet dysregulation in Alzheimer’s disease
Canobbio, I., Abubaker, A. A., Visconte, C., Torti, M., & Pula, G. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00065 · Cited by 101 · see citing works
Glycation as an atherogenic modification of LDL
Younis, N. N., Sharma, R., Soran, H., Charlton-Menys, V., Elseweidy, M. M., & Durrington, P. N. (2008) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328306a057 · Cited by 102 · see citing works
AGE–RAGE stress: a changing landscape in pathology and treatment of Alzheimer’s disease
Prasad, K. (2019) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-019-03553-4 · Cited by 96 · see citing works
Nϵ-Carboxymethyllysine in brain aging, diabetes mellitus, and Alzheimer's disease
Gironès, X., Guimerá, A., Cruz-Sánchez, C.-Z., Aznar, A. O., Sasaki, N., Makita, Z., Lafuente, J. V., Kalaria, R. N., & Cruz-Sánchez, F. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.02.006 · Cited by 95 · see citing works
Self-citationAskarova, S., Yang, X., Sheng, W., Sun, G. Y., & Lee, J. C.-M. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.09.038 · Cited by 92 · see citing works
Glucagon like peptide-1 (GLP-1) likes Alzheimer’s disease
Simsir, I. Y., Soyaltın, U. E., & Çetinkalp, Ş. (2018) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2018.03.002 · Cited by 92 · see citing works
Molecular Characteristics of RAGE and Advances in Small-Molecule Inhibitors
Kim, H. J., Jeong, M. S., & Jang, S. B. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22136904 · Cited by 92 · see citing works
Promiscuous Roles of Autophagy and Proteasome in Neurodegenerative Proteinopathies
Limanaqi, F., Biagioni, F., Gambardella, S., Familiari, P., Frati, A., & Fornai, F. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21083028 · Cited by 93 · see citing works
Altered expression of Aβ metabolism-associated molecules from d-galactose/AlCl3 induced mouse brain
Luo, Y., Niu, F., Sun, Z.-Z., Cao, W., Zhang, X., Guan, D., Lv, Z., Zhang, B., & Xu, Y. (2008) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2008.12.005 · Cited by 91 · see citing works
Kidney, heart and brain: three organs targeted by ageing and glycation
Frimat, M., Daroux, M., Litke, R., Nevière, R., Tessier, F. J., & Boulanger, E. (2017) · Clinical Science · doi:10.1042/cs20160823 · Cited by 88 · see citing works
Glyceraldehyde-derived advanced glycation end products in Alzheimer?s disease
Choei, H., Sasaki, N., Takeuchi, M., Yoshida, T., Ukai, W., Yamagishi, S., Kikuchi, S., & Saito, T. (2004) · Acta Neuropathologica · doi:10.1007/s00401-004-0871-x · Cited by 86 · see citing works
Self-citationMonteiro, C., Miarka, L., Perea-García, M., Priego, N., García‐Gómez, P., Álvaro‐Espinosa, L., de Pablos-Aragoneses, A., Yebra, N., Retana, D., Baena, P., et al. (2022) · Nature Medicine · doi:10.1038/s41591-022-01749-8 · Cited by 85 · see citing works
Current Treatment and Recent Clinical Research in Alzheimer's Disease
Neugroschl, J. A., & Sano, M. (2010) · Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine · doi:10.1002/msj.20165 · Cited by 83 · see citing works
Calfee, C. S., Budev, M. M., Matthay, M. A., Church, G. D., Brady, S. E., Uchida, T., Ishizaka, A., Lara, A., Ranes, J. L., Decamp, M., et al. (2007) · The Journal of Heart and Lung Transplantation · doi:10.1016/j.healun.2007.04.002 · Cited by 82 · see citing works
A Review on Potential Mechanisms of Terminalia chebula in Alzheimer’s Disease
Afshari, A. R., Sadeghnia, H. R., & Mollazadeh, H. (2016) · Advances in Pharmacological Sciences · doi:10.1155/2016/8964849 · Cited by 80 · see citing works
Meneghini, V., Bortolotto, V., Francese, M. T., Dellarole, A., Carraro, L., Terzieva, S., & Grilli, M. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.2052-12.2013 · Cited by 79 · see citing works
Walker, D. G., Lue, L. F., Paul, G., Patel, A., & Sabbagh, M. N. (2015) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2015.1001490 · Cited by 77 · see citing works
Moghaddam, H. S., Sherbaf, F. G., & Aarabi, M. H. (2019) · Frontiers in Neuroendocrinology · doi:10.1016/j.yfrne.2019.100782 · Cited by 74 · see citing works
Quan, Q.-K., Wang, J., Li, X., & Wang, Y. (2013) · PLoS ONE · doi:10.1371/journal.pone.0059155 · Cited by 77 · see citing works
Danger-Sensing/Patten Recognition Receptors and Neuroinflammation in Alzheimer’s Disease
Chiarini, A., Armato, U., Hu, P., & Prà, I. D. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21239036 · Cited by 75 · see citing works
Perrotta, M., Lembo, G., & Carnevale, D. (2016) · International Journal of Molecular Sciences · doi:10.3390/ijms17030347 · Cited by 74 · see citing works
BHAWAL, U. K., Ozaki, Y., Nishimura, M., Sugiyama, M., Sasahira, T., Nomura, Y., Sato, F., Fujimoto, K., Sasaki, N., Ikeda, M., et al. (2005) · Oncology · doi:10.1159/000087910 · Cited by 71 · see citing works
Self-citationViejo, L., Noori, A., Merrill, E., Das, S., Hyman, B. T., & Serrano‐Pozo, A. (2022) · Neuropathology and Applied Neurobiology · doi:10.1111/nan.12753 · Cited by 69 · see citing works
Juranek, J. K., Daffu, G. K., Wojtkiewicz, J., Lacomis, D., Kofler, J., & Schmidt, A. M. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00485 · Cited by 66 · see citing works
The p38MAPK-MK2 Signaling Axis as a Critical Link Between Inflammation and Synaptic Transmission
Beamer, E. H., & Corrêa, S. A. L. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.635636 · Cited by 64 · see citing works
Obesity and Diabetes Mediated Chronic Inflammation: A Potential Biomarker in Alzheimer’s Disease
Khan, M. S. H., & Hegde, V. K. (2020) · Journal of Personalized Medicine · doi:10.3390/jpm10020042 · Cited by 64 · see citing works
Ponce-Lopez, T. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26094209 · Cited by 75 · see citing works
- Authors
- Sasaki, N., Toki, S., Chowei, H., Saito, T., Nakano, N., Hayashi, Y., Takeuchi, M., & Makita, Z.
- Affiliations
- Sapporo Medical University (JP)
- Hokuriku University (JP)
- Kurume University (JP)
- Corresponding author
- Sasaki, Nobuyuki
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 2001-01
- Volume
- 888
- Issue
- 2
- Pages
- 256-262
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2091657472
- Cited by
- 253
- References
- 29
- Citations by year
- 2026: 2 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 12 · 2021: 15 · 2020: 13 · 2019: 10 · 2018: 8 · 2017: 7 · 2016: 11 · 2015: 10 · 2014: 13 · 2013: 20 · 2012: 8
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Advanced Glycation End Products research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- receptor for advanced glycation end products, advanced glycation end products, Alzheimer's disease, amyloid-beta, astrocytes, hippocampal neurons, diabetes mellitus, lysosomal degradation, colocalization, neuronal dysfunction
- MeSH terms
- Receptor for Advanced Glycation End Products, Aged, Alzheimer Disease, Animals, Antibody Specificity, Astrocytes, Cattle, Diabetes Mellitus, Female, Humans, Immunohistochemistry, Male, Middle Aged, Neurons, Receptors, Immunologic, Blotting, Western, Amyloid beta-Peptides, Glycation End Products, Advanced
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