Several epidemiological studies have reported moderately increased risks of Alzheimer’s disease (AD) in diabetic patients compared with general population. In diabetes mellitus, the formation and accumulation of advanced glycation end products (AGEs) progress more rapidly. Recent understanding of this process has confirmed that interactions between AGEs and their receptor (RAGE) may play a role in the pathogenesis of diabetic complications and AD. The authors have recently found that glyceraldehyde-derived AGEs (AGE- 2), which is predominantly the structure of toxic AGEs (TAGE), show significant toxicity on cortical neuronal cells and that the neurotoxic effect of diabetic serum is completely blocked by neutralizing antibody against the AGE-2 epitope. Moreover, in human AD brains, AGE-2 is distributed in the cytosol of neurons in the hippocampus and parahippocampal gyrus. These results suggest that TAGE is involved in the pathogenesis of AD as well as other age-related diseases. In this review, the authors discuss the molecular mechanisms of AD, especially focusing on TAGE-RAGE system.
Selkoe DJ.Normal and abnormal biology of the β-amyloid precursor protein. Annu Rev Neurosci. 1994;17: 489-517.
2.
Grundke-Iqbal I, Iqbal K, Quinlan M, Tung YC, Zaidi MS, Wisniewski HM.Microtubule-associated protein tau: a component of Alzheimer paired helical filaments. J Biol Chem. 1986;261:6084-6089.
3.
Ihara Y, Nukina N, Miura R, Ogawara M.Phosphorylated tau protein is integrated into paired helical filaments in Alzheimer’s disease. J Biochem. 1986;99:1807-1810.
4.
Iqbal K, Grundke-Iqbal I, Smith AJ, George L, Tung YC, Zaidi T.Identification and localization of a tau peptide to paired helical filaments of Alzheimer disease. Proc Natl Acad Sci U S A. 1989;86:5646-5650.
5.
Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM.Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999;53: 1937-1942.
6.
Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R.Diabetes mellitus and risk of Alzheimer’s disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol.2001;154:635-641.
7.
Peila R, Rodriguez BL, Launer LJ.Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes. 2002;51:1256-1262.
8.
Luchsinger JA, Reitz C, Honig LS, Tang MX, Shea S, Mayeux R.Aggregation of vascular risk factors and risk of incident Alzheimer disease. Neurology. 2005;65:545-551.
9.
Podolsky S, Leopold NA, Sax DS.Increased frequency of diabetes mellitus in patients with Huntington’s chorea. Lancet. 1972;299:1356-1359.
10.
Ristow M, Giannakidou E, Hebinck J, et al.An association between NIDDM and a GAA trinucleotide repeat polymorphism in the X25/frataxin (Friedreich’s ataxia) gene. Diabetes. 1998;47:851-854.
Moxley RT, Corbett AJ, Minaker KL, Rowe JW.Whole body insulin resistance in myotonic dystrophy. Ann Neurol. 1984;15: 157-162.
13.
Vlassara H, Brownlee M, Cerami A.Accumulation of diabetic rat peripheral nerve myelin by macrophages increases with the presence of advanced glycosylation endproducts. J Exp Med. 1984;160:197-207.
14.
Maillard LC.Action des acides aminés sur les sucres: formation des mélanoïdines par voie méthodique. C R Acad Sci. 1912;154: 66-68.
15.
Njoroge FG, Monnier VM.The chemistry of the Maillard reaction under physiological conditions: a review. Prog Clin Biol Res. 1989;304:85-107.
16.
Al-Abed Y, Bucala R.Structure of a synthetic glucose derived advanced glycation end-product that is immuno-logically cross-reactive with its naturally occurring counterparts. Bioconjug Chem. 2000;11:39-45.
17.
Reddy S, Bichler J, Wells-Knecht KJ, Thorpe SR, Baynes JW.Ne-(carboxymethyl) lysine is a dominant advanced glycation end product (AGE) antigen in tissue proteins. Biochemistry. 1995;34:10872-10878.
18.
Baynes JW, Thorpe SR.Role of oxidative stress in diabetic complications: a new perspective on an old paradigm. Diabetes. 1999;48:1-9.
19.
Glomb MA, Monnier VM.Mechanism of protein modification by glyoxal and glycolaldehyde, reactive intermediates of the Maillard reaction. J Biol Chem. 1995;270:10017-10026.
20.
Yamagishi S, Takeuchi M, Inagaki Y, Nakamura K, Imaizumi T.Role of advanced glycation end products (AGEs) and their receptor (RAGE) in the pathogenesis of diabetic microangiopathy. Int J Clin Pharmacol Res. 2003;23:129-134.
Sato T, Iwaki M, Shimogaito N, Wu X, Yamagishi S, Takeuchi M.TAGE (toxic AGEs) theory in diabetic complications. Curr Mol Med. In press.
23.
Vitek MP, Bhattacharya K, Glendening JM, et al.Advanced glycation end products contribute to amyloidosis in Alzheimer disease. Proc Nail Acad Sci U S A. 1994;91:4766-4770.
24.
Ledesma MD, Bonary P, Colaco C, Avila J.Analysis of microtuble-associated protein tau glycation in paired helical filaments. J Biol Chem. 1994;269:21614-21619.
25.
Yan SD, Chen X, Schmidt AM, et al.Glycated tau protein in Alzheimer disease: a mechanism for induction of oxidant stress. Proc Natl Acad Sci U S A. 1994;91:7787-7791.
26.
Takeuchi M, Bucala R, Suzuki T, et al.Neurotoxicity of advanced glycation end-products for cultured cortical neurons. J Neuropathol Exp Neurol. 2000;59: 1094-1105.
27.
Yamagishi S, Amano S, Inagaki Y, et al.Advanced glycation end products-induced apoptosis and overexpression of vascular endothelial growth factor in bovine retinal pericytes. Biochem Biophys Res Comm. 2002;290: 973-978.
28.
Yamagishi S, Inagaki Y, Okamoto T, et al.Advanced glycation end product-induced apoptosis and overexpression of vascular endothelial growth factor and monocyte chemoattractant protein-1 in human cultured mesangial cells. J Biol Chem. 2002;277: 20309-20315.
29.
Sekido H, Suzuki T, Jomori T, Takeuchi M, Yabe-Nishimura C, Yagihashi S.Reduced cell replication and induction of apoptosis by advanced glycation end products in rat Schwann cells. Biochem Biophys Res Comm. 2004;320:241-248.
30.
Abe R, Shimizu T, Sugawara H, et al.Regulation of human melanoma growth and metastasis by AGE-AGE receptor interactions. J Invest Dermat. 2004;122:461-467.
31.
Bucala R, Cerami A.Advanced glycosylation: chemistry, biology, and implications for diabetes and aging. Adv Pharmacol. 1992;23:1-34.
32.
Vlassara H, Bucala R, Striker L.Pathogenic effects of advanced glycosylation: biochemical, biologic, and clinical implications for diabetes and aging. Lab Invest. 1994;70:138-151.
33.
Brownlee M.Advanced protein glycosylation in diabetes and aging. Annu Rev Med. 1995;46:223-234.
Al-Abed Y, Kapurniotu A, Bucala R.Advanced glycation end products: detection and reversal. Methods Enzymol. 1999;309: 152-172.
36.
Monnier VM, Cerami A.Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science. 1981;211:491-493.
37.
Brownlee M, Cerami A, Vlassara H.Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med. 1988;318:1315-1321.
38.
Wells-Knecht KJ, Zyzak DV, Litchfield JE, Thorpe SR, Baynes JW.Mechanism of autoxidative glycosylation: identification of glyoxal and arabinose as intermediates in the autoxidative modification of proteins by glucose. Biochemistry. 1995;34: 3702-3709.
39.
Thornalley PJ.Pharmacology of methylglyoxal: formation, modification of proteins and nucleic acids, and enzymatic detoxification—a role in pathogenesis and antiproliferative chemotherapy. Gen Pharmacol. 1996;27:565-573.
40.
Thornalley PJ, Langborg A, Minhas HS.Formation of glyoxal, methylglyoxal and 3-deoxyglucosone in the glycation of proteins by glucose. Biochem J. 1999;344:109-116.
41.
Takeuchi M, Makita Z, Yanagisawa K, Kameda Y, Koike T.Detection of noncarboxymethyllysine and carboxymethyllysine advanced glycation end products (AGE) in serum of diabetic patients. Mol Med. 1999;5:393-405.
42.
Takeuchi M, Makita Z, Bucala R, Suzuki T, Koike T, Kameda Y.Immunological evidence that non-carboxymethyllysine advanced glycation end-products are produced from short chain sugars and dicarbonyl compounds in vivo. Mol Med. 2000;6:114-125.
43.
Takeuchi M, Yanase Y, Matsuura N, et al.Immunological detection of a novel advanced glycation end-product. Mol Med. 2001;7: 783-791.
44.
Takeuchi M, Makita Z.Alternative routes for the formation of immunochemically distinct advanced glycation end-products in vivo. Curr Mol Med. 2001;1:305-315.
45.
Koga K, Yamagishi S, Okamoto T, et al.Serum levels of glucose-derived advanced glycation end products are associated with the severity of diabetic retinopathy in type 2 diabetic patients without renal dysfunction. Int J Clin Pharmacol Res. 2002;22:13-17.
46.
Miura J, Yamagishi S, Uchigata Y, et al.Serum levels of non-carboxymethyllysine advanced glycation endproducts are correlated to severity of microvascular complications in patients with type 1 diabetes. J Diabetes Complications. 2003;17:16-21.
47.
Miura J, Uchigata Y, Yamamoto Y, et al.AGE down-regulation of monocyte RAGE expression and its association with diabetic complications in type 1 diabetes. J Diabetes Complications. 2004;18:53-59.
48.
Yokoi M, Yamagishi S, Takeuchi M, et al.Elevations of AGE and vascular endothelial growth factor with decreased total antioxidant status in the vitreous fluid of diabetic patients with retinopathy. Br J Ophthalmol. 2005;89:673-675.
49.
Sano H, Nagai R, Matsumoto K, Horiuchi S.Receptors for proteins modified by advanced glycation endproducts (AGE)-their functional role in atherosclerosis. Mech Ageing Dev. 1999;107:333-346.
50.
Schmidt AM, Yan SD, Yan SF, Stern DM.The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta. 2000;1498:99-111.
51.
Vlassara H.The AGE-receptor in the pathogenesis of diabetic complications. Diabetes Metab Res Rev. 2001;17:436-443.
52.
Ramasamy R, Vannucci SJ, Yan SS, Herold K, Yan SF, Schmidt AM.Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation. Glycobiology. 2005;15:16R-28R.
53.
Schmidt AM, Hori O, Brett J, Yan SD, Wautier JL, Stern D.Cellular receptors for advanced glycation end products: implications for induction of oxidant stress and cellular dysfunction in the pathogenesis of vascular lesions. Arterioscler Thromb.1994;14:1521-1528.
54.
Li YM, Mitsuhashi T, Wojciechowicz D, et al.Molecular identity and cellular distribution of advanced glycation endproduct receptors: relationship of p60 to OST-48 and p90 to 80K-H membrane proteins. Proc Natl Acad Sci U S A. 1996;93:11047-11052.
55.
Vlassara H, Li YM, Imani F, et al.Identification of galectin-3 as a high-affinity binding protein for advanced glycation end products (AGE): a new member of the AGE-receptor complex. Mol Med. 1995;1:634-646.
56.
Ohgami N, Nagai R, Ikemoto M, et al.CD36, serves as a receptor for advanced glycation endproducts (AGE). J Diabetes Complications. 2002;16:56-59.
57.
el Khoury J, Thomas CA, Loike JD, Hickman SE, Cao L, Silverstein SC.Macrophages adhere to glucose-modified basement membrane collagen IV via their scavenger receptors. J Biol Chem. 1994;269:10197-10200.
58.
Tamura Y, Adachi H, Osuga J, et al.FEEL-1 and FEEL- 2 are endocytic receptors for advanced glycation end products. J Biol Chem. 2003;278:12613-12617.
59.
Hudson BI, Bucciarelli LG, Wendt T, et al.Blockade of receptor for advanced glycation end products: a new target for therapeutic intervention in diabetic complications and inflammatory disorders. Arch Biochem Biophys. 2003;419:80-88.
60.
Yonekura H, Yamamoto Y, Sakurai S, et al.RAGE engagement and vascular cell derangement by short chain sugar-derived advanced glycation end products. Int Congr Ser. 2002;1245:129-135.
61.
Yonekura H, Yamamoto Y, Sakurai S, et al.Novel splice variants of the receptor for advanced glycation end-products expressed in human vascular endothelial cells and pericytes, and their putative roles in diabetes-induced vascular injury. Biochem J. 2003;370:1097-1109.
62.
Yan SD, Chen X, Fu J, et al.RAGE and amyloid-β peptide neurotoxicity in Alzheimer’s disease. Nature. 1996;382:685-691.
63.
Schmidt AM, Yan SD, Yan SF, Stern DM.The biology of the receptor for advanced glycation end products and its ligands. Biochim Biophys Acta. 2000;1498:99-111.
64.
Bucciarelli LG, Wendt T, Rong L, et al.RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell Mol Life Sci. 2002;59: 1117-1128.
65.
Yan SD, Zhu H, Fu J, et al.Amyloid-β peptide-receptor for advanced glycation endproduct interaction elicits neuronal expression of macrophage-colony stimulating factor: a proinflammatory pathway in Alzheimer disease. Proc Natl Acad Sci U S A. 1997;94:5296-5301.
66.
Arancio O, Zhang HP, Chen X, et al.RAGE potentiates Aβ-induced perturbation of neuronal function in transgenic mice. EMBO J. 2004;23:4096-4105.
67.
Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA.Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004;61:661-666.
68.
Luchsinger JA, Tang MX, Shea S, Mayeux R.Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004;63:1187-1192.
69.
Gasparini L, Netzer WJ, Greengard P, Xu H.Does insulin dysfunction play a role in Alzheimer’s disease?Trends Pharmacol Sci. 2002;23:288-293.
70.
Gasparini L, Xu H.Potential roles of insulin and IGF-1 in Alzheimer’s disease. Trends Neurosci. 2003;26:404-406.
71.
Watson GS, Peskind ER, Asthana S, et al.Insulin increases CSF Aβ42 levels in normal older adults. Neurology. 2003;60:1899-1903.
72.
Watson GS, Craft S.The role of insulin resistance in the pathogenesis of Alzheimer’s disease: implications for treatment. CNS Drugs. 2003;17:27-45.
73.
Munch G, Schinzel R, Loske C, et al.Alzheimer’s disease-synergistic effects of glucose deficit, oxidative stress and advanced glycation endproducts. J Neural Transm. 1998;105:439-461.
74.
Makita Z, Bucala R, Rayfield EJ, et al.Reactive glycosylation endproducts in diabetic uraemia and treatment of renal failure. Lancet. 1994;343:1519-1522.
75.
Harrington CR, Wischik CM, McArthur FK, Taylor GA, Edwardson JA, Candy JM.Alzheimer’s-disease-like changes in tau protein processing: association with aluminium accumulation in brains of renal dialysis patients. Lancet. 1994;343:993-997.
76.
Riviere S, Birlouez-Aragon I, Vellas B.Plasma protein glycation in Alzheimer’s disease. Glycoconj J. 1998;15: 1039-1042.
77.
Shuvaev VV, Laffont I, Serot JM, Fujii J, Taniguchi N, Siest G.Increased protein glycation in cerebrospinal fluid of Alzheimer’s disease. Neurobiol Aging. 2001;22: 397-402.
78.
Yamagishi S, Amano S, Inagaki Y, Okamoto T, Takeuchi M, Makita Z.Beraprost sodium, a prostaglandin I2 analogue, protects against advanced glycation end products-induced injury in cultured retinal pericytes. Mol Med. 2002;8:546-550.
79.
Yamagishi S, Takeuchi M, Matsui T, Nakamura K, Imaizumi T, Inoue H.Angiotensin II augments advanced glycation end product-induced pericyte apoptosis through RAGE overexpression. FEBS Lett. 2005;579:4265-4270.
80.
Okamoto T, Yamagishi S, Inagaki Y, et al.Incadronate disodium inhibits advanced glycation end products-induced angiogenesis in vitro. Biochem Biophys Res Comm. 2002;297:419-424.
81.
Okamoto T, Yamagishi S, Inagaki Y, et al.Angiogenesis induced by advanced glycation end products and its prevention by cerivastatin. FASEB J. 2002;16:1928-1930.
82.
Vlassara H.Protein glycation in the kidney: role in diabetes and aging. Kidney Int. 1996;49:1795-1804.
83.
Stitt AW.Advanced glycation: an important pathological event in diabetic and age related ocular disease. Br J Ophthalmol. 2001;85:746-753.
84.
Tilton RG.Diabetic vascular dysfunction: links to glucose-induced reductive stress and VEGF. Microsc Res Tech. 2002;57:390-407.
85.
Thornalley PJ.Glycation in diabetic neuropathy: characteristics, consequences, causes, and therapeutic options. Int Rev Neurobiol. 2002;50:37-57.
86.
Basta G, Lazzerini G, Massaro M, et al.Advanced glycation end products activate endothelium through signal-transduction receptor RAGE: a mechanism for amplification of inflammatory responses. Circulation. 2002;105:816-822.
87.
Vlassara H.Advanced glycation end-products and atherosclerosis. Ann Med. 1996;28:419-426.
88.
Stitt AW, Bucala R, Vlassara H.Atherogenesis and advanced glycation: promotion, progression, and prevention. Ann N Y Acad Sci. 1997;811:115-127.
89.
Baynes JW, Thorpe SR.Glycoxidation and lipoxidation in atherogenesis. Free Rad Biol Med. 2000;28:1708-1716.
90.
Bucciarelli LG, Wendt T, Qu W, et al.RAGE blockade stabilizes established atherosclerosis in diabetic apolipoprotein E-null mice. Circulation. 2002;106:2827-2835.
91.
Huttunen HJ, Fages C, Kuja-Panula J, Ridley AJ, Rauvala H.Receptor for advanced glycation end products-binding COOH-terminal motif of amphoterin inhibits invasive migration and metastasis. Cancer Res. 2002;62:4805-4811.
92.
Kuniyasu H, Oue N, Wakikawa A, et al.Expression of receptors for advanced glycation end-products (RAGE) is closely associated with the invasive and metastatic activity of gastric cancer. J Pathol. 2002;196:163-170.
93.
Stopper H, Schinzel R, Sebekova K, Heidland A.Genotoxicity of advanced glycation end products in mammalian cells. Cancer Lett. 2003;190:151-156.
94.
Sasaki N, Fukatsu R, Tsuzuki K, et al.Advanced glycation end products in Alzheimer’s disease and other neurode-generative diseases. Am J Pathol. 1998;153:1149-1155.
95.
Lue LF, Yan SD, Stern D, Walker DG.Preventing activation of receptor for advanced glycation endproducts in Alzheimer’s disease. Curr Drug Targets CNS Neurol Disord. 2005;4:249-266.
96.
Richter T, Munch G, Luth HJ, et al.Immunochemical crossreactivity of antibodies specific for “advanced glycation endproducts” with “advanced lipoxidation end-products.”Neurobiol Aging. 2005; 26:465-474.
97.
Ahmed N, Ahmed U, Thornalley PJ, Hager K, Fleischer G, Munch G.Protein glycation, oxidation and nitration adduct residues and free adducts of cerebrospinal fluid in Alzheimer’s disease and link to cognitive impairment. J Neurochem. 2005;92:255-263.
98.
Schmitt HP.ε-Glycation, APP and Aβ in ageing and Alzheimer’s disease: a hypothesis. Med Hypotheses. 2006;66:898-906.
99.
Takeuchi M, Kikuchi S, Sasaki N, et al.Involvement of advanced glycation end-products (AGEs) in Alzheimer’s disease. Curr Alzheimer Res. 2004;1:39-46.
100.
Tatton N: Increased caspase 3 and Bax immunoreactivity accompany nuclear GAPDH translocation and neuronal apoptosis in Parkinson’s disease. Exp Neurol. 2000;166:29-43.
101.
Senatorov V, Charles V, Reddy P, Tagle D, Chuang D.Overexpression and nuclear accumulation of glyceraldehyde- 3-phosphate dehydrogenase in a transgenic mouse model of Huntington’s disease. Mol Cell Neurosci. 2003;22:285-297.
102.
Mazzola JL, Sirover MA.Subcellular alteration of glyceraldehyde-3-phosphate dehydrogenase in Alzheimer’s disease fibroblasts. J Neurosci Res. 2003;71:279-285.
103.
Ishitani R, Sunaga K, Hirano A, Saunders P, Katsube N, Chuang D.Evidence that glyceraldehyde-3- phosphate dehydrogenase is involved in age-induced apoptosis in mature cerebellar neurones in culture. J Neurochem. 1996;66:928-935.
104.
Sawa A, Khan A, Hester L, Snyder S.Glyceraldehyde- 3-phosphate dehydrogenase: nuclear translocation participates in neuronal and nonneuronal cell death. Proc Natl Acad Sci U S A. 1997;94:11669-11674.
105.
Ishitani R, Tanaka M, Sunaga K, Katsube N, Chuang D.Nuclear localization of overexpressed glyceralde-hyde-3-phosphate dehydrogenase in culture cerebellar neurons undergoing apoptosis. Mol Pharmacol. 1998;53:701-707.
106.
Dastoor Z, Dreyer J.Potential role of nuclear translocation of glyceraldehyde-3-phosphate dehydrogenase in apoptosis and oxidative stress. J Cell Sci. 2001;114: 1643-1653.
107.
Woltjer RL, Maezawa I, Ou JJ, Montine KS, Montine TJ.Advanced glycation endproduct precursor alters intracellular amyloid-β/AβPP carboxy-terminal fragment aggregation and cytotoxicity. J Alzheimer Dis.2003;5:467-476.
108.
Smith MA, Taneda S, Richey PL, et al.Advanced Maillard reaction end products are associated with Alzheimer disease pathology. Proc Natl Acad Sci U S A.1994;91:5710-5714.
109.
Yan SD, Yan SF, Chen X, et al.Non-enzymatically glycated tau in Alzheimer’s disease induces neuronal oxidant stress resulting in cytokine gene expression and release of amyloid β-peptide. Nat Med. 1995;1:693-699.
110.
Sasaki N, Toki S, Chowei H, et al.Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer’s disease. Brain Res. 2001;888:256-262.
111.
Girones X, Guimera A, Cruz-Sanchez CZ, et al.Nε-carboxymethyllysine in brain aging, diabetes mellitus, and Alzheimer’s disease. Free Rad Biol Med. 2004;36: 1241-1247.
112.
Luth HJ, Ogunlade V, Kuhla B, et al.Age- and stage-dependent accumulation of advanced glycation end products in intracellular deposits in normal and Alzheimer’s disease brains. Cereb Cortex. 2005;15: 211-220.
113.
Choei H, Sasaki N, Takeuchi M, et al.Glyceraldehyde-derived advanced glycation end products in Alzheimer’s disease. Acta Neuropathol. 2004;108:189-193.
114.
Takeuchi M, Yamagishi S.Alternative routes for the formation of glyceraldehyde-derived AGEs (TAGE) in vivo. Med Hypotheses.2004;63:453-455.
115.
Schalkwijk CG, Stehouwer CD, van Hinsbergh VW.Fructose-mediated non-enzymatic glycation: sweet coupling or bad modification. Diabetes Metab Res Rev. 2004;20:369-382.
116.
Wong A, Luth HJ, Deuther-Conrad W, et al.Advanced glycation endproducts co-localize with inducible nitric oxide synthase in Alzheimer’s disease. Brain Res. 2001;920:32-40.
117.
Reddy VP, Obrenovich ME, Atwood CS, Perry G, Smith MA.Involvement of Maillard reactions in Alzheimer disease. Neurotox Res. 2002;4:191-209.
118.
Usui T, Hayase F.Isolation and identification of the 3- hydroxy-5-hydroxymethyl-pyridinium compound as a novel advanced glycation end product on glyceralde-hyde-related Maillard reaction. Biosci Biotechnol Biochem. 2003;67:930-932.
119.
Tessier FJ, Monnier VM, Sayre LM, Kornfield JA.Triosidines: novel Maillard reaction products and cross-links from the reaction of triose sugars with lysine and arginine residues. Biochem J. 2003;369: 705-719.
120.
Nagai R, Hayashi CM, Xia L, Takeya M, Horiuchi S.Identification in human atherosclerotic lesions of GA-pyridine, a novel structure derived from glycolaldehyde-modified proteins. J Biol Chem. 2002;277:48905-48912.
121.
Yamagishi S, Nakamura K, Inoue H, Kikuchi S, Takeuchi M.Possible participation of advanced glycation end products in the pathogenesis of colorectal cancer in diabetic patients. Med Hypotheses. 2005;64:1208-1210.
122.
Ripova D, Strunecka A.An ideal biological marker of Alzheimer’s disease: dream or reality?Physiol Res. 2001;50: 119-129.
