Consequences of aberrant insulin regulation in the brain: Can treating diabetes be effective for Alzheimer's disease

Current Neuropharmacology

Volumn 9, Issue 4, 2011, Pages 693-705

  Arab, L ^a   Sadeghi, R ^b   Walker, D G ^a   Lue, L F ^a   Sabbagh, M N ^a  

^a SUN HEALTH RESEARCH INSTITUTE   (United States)

^b MIDWESTERN UNIVERSITY   (United States)

Author keywords

Alzheimer's disease; Amyloid beta; Glucose metabolism; Neurodegeneration; Pathology

Indexed keywords

2,4 THIAZOLIDINEDIONE DERIVATIVE; ADVANCED GLYCATION END PRODUCT; APOLIPOPROTEIN E4; GLUCOSE; INSULIN; INSULIN RECEPTOR; INSULINASE; NONSTEROID ANTIINFLAMMATORY AGENT; ORAL ANTIDIABETIC AGENT; PIOGLITAZONE; PLACEBO; ROSIGLITAZONE; SOMATOMEDIN;

ALZHEIMER DISEASE; CELL SURVIVAL; CENTRAL NERVOUS SYSTEM; CLINICAL FEATURE; DIABETES MELLITUS; DISEASE ASSOCIATION; DISEASE EXACERBATION; GLUCOSE METABOLISM; HUMAN; HYPERTENSION; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RESISTANCE; MULTIINFARCT DEMENTIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; REVIEW;

EID: 82955245622     PISSN: 1570159X     EISSN: 18756190     Source Type: Journal    
DOI: 10.2174/157015911798376334     Document Type: Review

References (169)

1. Hebert, L. E.; Scherr, P. A.; Bienias, J. L.; Bennett, D. A.; Evans, D. A. Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch. Neurol., 2003, 60, 1119 1122.
2. Hebert, L. E.; Beckett, L. A.; Scherr, P. A.; Evans, D. A. Annual incidence of Alzheimer disease in the United States projected to the years 2000 through 2050. Alzheimer Dis. Assoc. Disord., 2001, 15, 169-173.
3. Bianchetti, A.; Ranieri, P.; Margiotta, A.; Trabucchi, M. Pharmacological treatment of Alzheimer's Disease. Aging Clin. Exp. Res., 2006, 18, 158-162.
4. Karow, D. S.; McEvoy, L. K.; Fennema-Notestine, C.; Hagler, D. J., Jr.; Jennings, R. G.; Brewer, J. B.; Hoh, C. K.; Dale, A. M. Relative Capability of MR Imaging and FDG PET to Depict Changes Associated with Prodromal and Early Alzheimer Disease. Radiology, 2010, 256, 932-942.
5. Mosconi, L.; Berti, V.; Glodzik, L.; Pupi, A.; De, S. S.; de Leon, M. J. Pre-clinical detection of Alzheimer's disease using FDG-PET, with or without amyloid imaging. J. Alzheimers Dis., 2010, 20, 843-854.
6. Hoffman, J. M.; Guze, B. H.; Baxter, L. R.; Mazziotta, J. C.; Phelps, M. E. [18F]-fluorodeoxyglucose (FDG) and positron emission tomography (PET) in aging and dementia. A decade of studies. Eur. Neurol., 1989, 29(Suppl 3), 16-24.
7. Reger, M. A.; Watson, G. S.; Green, P. S.; Wilkinson, C. W.; Baker, L. D.; Cholerton, B.; Fishel, M. A.; Plymate, S. R.; Breitner, J. C.; DeGroodt, W.; Mehta, P.; Craft, S. Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology, 2008, 70, 440-448.
8. Beeri, M. S.; Silverman, J. M.; Davis, K. L.; Marin, D.; Grossman, H. Z.; Schmeidler, J.; Purohit, D. P.; Perl, D. P.; Davidson, M.; Mohs, R. C.; Haroutunian, V. Type 2 diabetes is negatively associated with Alzheimer's disease neuropathology. J. Gerontol. A Biol. Sci. Med. Sci., 2005, 60, 471-475.
9. Jagust, W. J.; Landau, S. M.; Shaw, L. M.; Trojanowski, J. Q.; Koeppe, R. A.; Reiman, E. M.; Foster, N. L.; Petersen, R. C.; Weiner, M. W.; Price, J. C.; Mathis, C. A. Relationships between biomarkers in aging and dementia. Neurology, 2009, 73, 1193 1199.
10. Langbaum, J. B.; Chen, K.; Lee, W.; Reschke, C.; Bandy, D.; Fleisher, A. S.; Alexander, G. E.; Foster, N. L.; Weiner, M. W.; Koeppe, R. A.; Jagust, W. J.; Reiman, E. M. Categorical and correlational analyses of baseline fluorodeoxyglucose positron emission tomography images from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Neuroimage., 2009, 45, 1107-1116.
11. Haense, C.; Buerger, K.; Kalbe, E.; Drzezga, A.; Teipel, S. J.; Markiewicz, P.; Herholz, K.; Heiss, W. D.; Hampel, H. CSF total and phosphorylated tau protein, regional glucose metabolism and dementia severity in Alzheimer's disease. Eur. J. Neurol., 2008, 15, 1155-1162.
12. Chertkow, H.; Black, S. Imaging biomarkers and their role in dementia clinical trials. Can. J. Neurol. Sci., 2007, 34(Suppl 1), S77-S83.
13. Rabinovici, G. D.; Jagust, W. J. Amyloid imaging in aging and dementia: testing the amyloid hypothesis in vivo. Behav. Neurol., 2009, 21, 117-128.
14. Petrie, E. C.; Cross, D. J.; Galasko, D.; Schellenberg, G. D.; Raskind, M. A.; Peskind, E. R.; Minoshima, S. Preclinical evidence of Alzheimer changes: convergent cerebrospinal fluid biomarker and fluorodeoxyglucose positron emission tomography findings. Arch. Neurol., 2009, 66, 632-637.
15. Mosconi, L.; Mistur, R.; Switalski, R.; Brys, M.; Glodzik, L.; Rich, K.; Pirraglia, E.; Tsui, W.; De, S. S.; de Leon, M. J. Declining brain glucose metabolism in normal individuals with a maternal history of Alzheimer disease. Neurology, 2009, 72, 513-520.
16. Caselli, R. J.; Chen, K.; Lee, W.; Alexander, G. E.; Reiman, E. M. Correlating cerebral hypometabolism with future memory decline in subsequent converters to amnestic pre-mild cognitive impairment. Arch. Neurol., 2008, 65, 1231-1236.
17. Mosconi, L.; Perani, D.; Sorbi, S.; Herholz, K.; Nacmias, B.; Holthoff, V.; Salmon, E.; Baron, J. C.; De Cristofaro, M. T.; Padovani, A.; Borroni, B.; Franceschi, M.; Bracco, L.; Pupi, A. MCI conversion to dementia and the APOE genotype: a prediction study with FDG-PET. Neurology, 2004, 63, 2332-2340.
18. Ishii, K.; Sasaki, H.; Kono, A. K.; Miyamoto, N.; Fukuda, T.; Mori, E. Comparison of gray matter and metabolic reduction in mild Alzheimer's disease using FDG-PET and voxel-based morphometric MR studies. Eur. J. Nucl. Med. Mol. Imaging, 2005, 32, 959-963.
19. Bingham, E. M.; Hopkins, D.; Smith, D.; Pernet, A.; Hallett, W.; Reed, L.; Marsden, P. K.; Amiel, S. A. The role of insulin in human brain glucose metabolism: an 18fluoro-deoxyglucose positron emission tomography study. Diabetes, 2002, 51, 3384-3390.
20. Kawasaki, K.; Ishii, K.; Saito, Y.; Oda, K.; Kimura, Y.; Ishiwata, K. Influence of mild hyperglycemia on cerebral FDG distribution patterns calculated by statistical parametric mapping. Ann. Nucl. Med., 2008, 22, 191-200.
21. Cardoso, S.; Correia, S.; Santos, R. X.; Carvalho, C.; Santos, M. S.; Oliveira, C. R.; Perry, G.; Smith, M. A.; Zhu, X.; Moreira, P. I. Insulin is a Two-Edged Knife on the Brain. J. Alzheimers Dis., 2009, 18, 483-507.
22. Gerozissis, K. Brain insulin, energy and glucose homeostasis; genes, environment and metabolic pathologies. Eur. J. Pharmacol., 2008, 585, 38-49.
23. Steen, E.; Terry, B. M.; Rivera, E. J.; Cannon, J. L.; Neely, T. R.; Tavares, R.; Xu, X. J.; Wands, J. R.; de la Monte, S. M. Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease--is this type 3 diabetes? J. Alzheimers Dis., 2005, 7, 63-80.
24. Ott, A.; Stolk, R. P.; Hofman, A.; van, H. F.; Grobbee, D. E.; Breteler, M. M. Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia, 1996, 39, 1392-1397.
25. Tanti, J. F.; Jager, J. Cellular mechanisms of insulin resistance: role of stress-regulated serine kinases and insulin receptor substrates (IRS) serine phosphorylation. Curr. Opin. Pharmacol., 2009, 9, 753-762.
26. Gogg, S.; Smith, U.; Jansson, P. A. Increased MAPK activation and impaired insulin signaling in subcutaneous microvascular endothelial cells in type 2 diabetes: the role of endothelin-1. Diabetes, 2009, 58, 2238-2245.
27. Boura-Halfon, S.; Zick, Y. Phosphorylation of IRS proteins, insulin action, and insulin resistance. Am. J. Physiol Endocrinol. Metab, 2009, 296, E581-E591.
28. Lebrun, P.; Van, O. E. SOCS proteins causing trouble in insulin action. Acta Physiol (Oxf), 2008, 192, 29-36.
29. Janson, J.; Laedtke, T.; Parisi, J. E.; O'Brien, P.; Petersen, R. C.; Butler, P. C. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes, 2004, 53, 474-481.
30. de la Monte, S. M.; Wands, J. R. Alzheimer's disease is type 3 diabetes-evidence reviewed. J. Diabetes Sci. Technol., 2008, 2, 1101-1113.
31. Bruehl, H.; Wolf, O. T.; Sweat, V.; Tirsi, A.; Richardson, S.; Convit, A. Modifiers of cognitive function and brain structure in middle aged and elderly individuals with type 2 diabetes mellitus. Brain Res., 2009, 1280, 186-194.
32. Pasquier, F.; Boulogne, A.; Leys, D.; Fontaine, P. Diabetes mellitus and dementia. Diabetes Metab., 2006, 32, 403-414.
33. Tiehuis, A. M.; Mali, W. P.; van Raamt, A. F.; Visseren, F. L.; Biessels, G. J.; van Zandvoort, M. J.; Kappelle, L. J.; van der, G. Y. Cognitive dysfunction and its clinical and radiological determinants in patients with symptomatic arterial disease and diabetes. J. Neurol. Sci., 2009, 283, 170-174.
34. de la Monte, S. M. Insulin resistance and Alzheimer's disease. BMB Rep., 2009, 42, 475-481.
35. Hallschmid, M.; Schultes, B. Central nervous insulin resistance: a promising target in the treatment of metabolic and cognitive disorders? Diabetologia, 2009, 52, 2264-2269.
36. Liao, F. F.; Xu, H. Insulin signaling in sporadic Alzheimer's disease. Sci. Signal., 2009, 2, e36.
37. Naderali, E. K.; Ratcliffe, S. H.; Dale, M. C. Obesity and Alzheimer's disease: a link between body weight and cognitive function in old age. Am. J. Alzheimers. Dis. Other Demen., 2009, 24, 445-449.
38. Salkovic-Petrisic, M.; Osmanovic, J.; Grunblatt, E.; Riederer, P.; Hoyer, S. Modeling Sporadic Alzheimer's Disease: The Insulin Resistant Brain State Generates Multiple Long-Term Morphobiological Abnormalities Inclusive Hyperphosphorylated Tau Protein and Amyloid-beta. A Synthesis. J. Alzheimers. Dis., 2009, 18(4): 729-750.
39. Zhao, W. Q.; Townsend, M. Insulin resistance and amyloidogenesis as common molecular foundation for type 2 diabetes and Alzheimer's disease. Biochim. Biophys. Acta, 2009, 1792, 482 496.
40. Starr, V. L.; Convit, A. Diabetes, sugar-coated but harmful to the brain. Curr. Opin. Pharmacol., 2007, 7, 638-642.
41. Grossman, H. Does diabetes protect or provoke Alzheimer's disease? Insights into the pathobiology and future treatment of Alzheimer's disease. CNS. Spectr., 2003, 8, 815-823.
42. Zhao, L.; Teter, B.; Morihara, T.; Lim, G. P.; Ambegaokar, S. S.; Ubeda, O. J.; Frautschy, S. A.; Cole, G. M. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J. Neurosci., 2004, 24, 11120-11126.
43. Yu, Y.; Kastin, A. J.; Pan, W. Reciprocal interactions of insulin and insulin-like growth factor I in receptor-mediated transport across the blood-brain barrier. Endocrinology, 2006, 147, 2611 2615.
44. Fernandez-Gamba, A.; Leal, M. C.; Morelli, L.; Castano, E. M. Insulin-degrading enzyme: structure-function relationship and its possible roles in health and disease. Curr. Pharm. Des., 2009, 15, 3644-3655.
45. Kojro, E.; Postina, R. Regulated proteolysis of RAGE and AbetaPP as possible link between type 2 diabetes mellitus and Alzheimer's disease. J. Alzheimers Dis., 2009, 16, 865-878.
46. Yamagishi, S.; Nakamura, K.; Matsui, T.; Noda, Y.; Imaizumi, T. Receptor for advanced glycation end products (RAGE): a novel therapeutic target for diabetic vascular complication. Curr. Pharm. Des., 2008, 14, 487-495.
47. Taguchi, A. Vascular factors in diabetes and Alzheimer's disease. J. Alzheimers. Dis., 2009, 16, 859-864.
48. Ma, Q. L.; Yang, F.; Rosario, E. R.; Ubeda, O. J.; Beech, W.; Gant, D. J.; Chen, P. P.; Hudspeth, B.; Chen, C.; Zhao, Y.; Vinters, H. V.; Frautschy, S. A.; Cole, G. M. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J. Neurosci., 2009, 29, 9078-9089.
49. Zhao, W. Q.; Lacor, P. N.; Chen, H.; Lambert, M. P.; Quon, M. J.; Krafft, G. A.; Klein, W. L. Insulin receptor dysfunction impairs cellular clearance of neurotoxic oligomeric a{beta}. J. Biol. Chem., 2009, 284, 18742-18753.
50. Jolivalt, C. G.; Lee, C. A.; Beiswenger, K. K.; Smith, J. L.; Orlov, M.; Torrance, M. A.; Masliah, E. Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer's disease and correction by insulin. J. Neurosci. Res., 2008, 86, 3265-3274.
51. Townsend, M.; Mehta, T.; Selkoe, D. J. Soluble Abeta inhibits specific signal transduction cascades common to the insulin receptor pathway. J. Biol. Chem., 2007, 282, 33305-33312.
52. Liao, F. F.; Xu, H. Insulin signaling in sporadic Alzheimer's disease. Sci. Signal., 2009, 2, e36.
53. Cardoso, S.; Correia, S.; Santos, R. X.; Carvalho, C.; Santos, M. S.; Oliveira, C. R.; Perry, G.; Smith, M. A.; Zhu, X.; Moreira, P. I. Insulin is a Two-Edged Knife on the Brain. J. Alzheimers. Dis., 2009, 18, 483-507.
54. Landreth, G. Therapeutic use of agonists of the nuclear receptor PPARgamma in Alzheimer's disease. Curr. Alzheimer Res., 2007, 4, 159-164.
55. Banks, W. A.; Jaspan, J. B.; Huang, W.; Kastin, A. J. Transport of insulin across the blood-brain barrier: saturability at euglycemic doses of insulin. Peptides, 1997, 18, 1423-1429.
56. Pardridge, W. M.; Eisenberg, J.; Yang, J. Human blood-brain barrier insulin receptor. J. Neurochem., 1985, 44, 1771-1778.
57. Frolich, L.; Blum-Degen, D.; Bernstein, H. G.; Engelsberger, S.; Humrich, J.; Laufer, S.; Muschner, D.; Thalheimer, A.; Turk, A.; Hoyer, S.; Zochling, R.; Boissl, K. W.; Jellinger, K.; Riederer, P. Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J. Neural Transm., 1998, 105, 423-438.
58. Frolich, L.; Blum-Degen, D.; Riederer, P.; Hoyer, S. A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease. Ann. N. Y. Acad. Sci., 1999, 893, 290-293.
59. Takahashi, M.; Yamada, T.; Tooyama, I.; Moroo, I.; Kimura, H.; Yamamoto, T.; Okada, H. Insulin receptor mRNA in the substantia nigra in Parkinson's disease. Neurosci. Lett., 1996, 204, 201-204.
60. Carro, E.; Torres-Aleman, I. The role of insulin and insulin-like growth factor I in the molecular and cellular mechanisms underlying the pathology of Alzheimer's disease. Eur. J. Pharmacol., 2004, 490, 127-133.
61. Holscher, C.; van, A. L.; Sutherland, C. Anaesthesia generates neuronal insulin resistance by inducing hypothermia. BMC Neurosci., 2008, 9, 100.
62. Baura, G. D.; Foster, D. M.; Kaiyala, K.; Porte, D., Jr.; Kahn, S. E.; Schwartz, M. W. Insulin transport from plasma into the central nervous system is inhibited by dexamethasone in dogs. Diabetes, 1996, 45, 86-90.
63. Hartge, M. M.; Unger, T.; Kintscher, U. The endothelium and vascular inflammation in diabetes. Diab. Vasc. Dis. Res., 2007, 4, 84-88.
64. Kotzke, G.; Schutt, M.; Missler, U.; Moller, D. E.; Fehm, H. L.; Klein, H. H. Binding of human, porcine and bovine insulin to insulin receptors from human brain, muscle and adipocytes and to expressed recombinant alternatively spliced insulin receptor isoforms. Diabetologia, 1995, 38, 757-763.
65. Roth, R. A.; Morgan, D. O.; Beaudoin, J.; Sara, V. Purification and characterization of the human brain insulin receptor. J. Biol. Chem., 1986, 261, 3753-3757.
66. Rees-Jones, R. W.; Hendricks, S. A.; Quarum, M.; Roth, J. The insulin receptor of rat brain is coupled to tyrosine kinase activity. J. Biol. Chem., 1984, 259, 3470-3474.
67. de la Monte, S. M.; Wands, J. R. Review of insulin and insulin-like growth factor expression, signaling, and malfunction in the central nervous system: relevance to Alzheimer's disease. J. Alzheimers. Dis., 2005, 7, 45-61.
68. Rivera, E. J.; Goldin, A.; Fulmer, N.; Tavares, R.; Wands, J. R.; de la Monte, S. M. Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: link to brain reductions in acetylcholine. J. Alzheimers Dis., 2005, 8, 247-268.
69. Neumann, K. F.; Rojo, L.; Navarrete, L. P.; Farias, G.; Reyes, P.; Maccioni, R. B. Insulin resistance and Alzheimer's disease: molecular links & clinical implications. Curr. Alzheimer Res., 2008, 5, 438-447.
70. den, H. T.; Vermeer, S. E.; van Dijk, E. J.; Prins, N. D.; Koudstaal, P. J.; Hofman, A.; Breteler, M. M. Type 2 diabetes and atrophy of medial temporal lobe structures on brain MRI. Diabetologia, 2003, 46, 1604-1610.
71. Nelson, P. T.; Smith, C. D.; Abner, E. A.; Schmitt, F. A.; Scheff, S. W.; Davis, G. J.; Keller, J. N.; Jicha, G. A.; Davis, D.; Wang-Xia, W.; Hartman, A.; Katz, D. G.; Markesbery, W. R. Human cerebral neuropathology of Type 2 diabetes mellitus. Biochim. Biophys. Acta, 2009, 1792, 454-469.
72. Sugimoto, K.; Murakawa, Y.; Sima, A. A. Diabetic neuropathy--a continuing enigma. Diabetes Metab Res. Rev., 2000, 16, 408-433.
73. Toth, C.; Martinez, J.; Zochodne, D. W. RAGE, diabetes, and the nervous system. Curr. Mol. Med., 2007, 7, 766-776.
74. Beeri, M. S.; Schmeidler, J.; Silverman, J. M.; Gandy, S.; Wysocki, M.; Hannigan, C. M.; Purohit, D. P.; Lesser, G.; Grossman, H. T.; Haroutunian, V. Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology, 2008, 71, 750-757.
75. Arvanitakis, Z.; Schneider, J. A.; Wilson, R. S.; Li, Y.; Arnold, S. E.; Wang, Z.; Bennett, D. A. Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology, 2006, 67, 1960-1965.
76. Bertram, L.; Tanzi, R. E. Genome-wide association studies in Alzheimer's disease. Hum. Mol. Genet., 2009, 18, R137-R145.
77. Beecham, G. W.; Martin, E. R.; Li, Y. J.; Slifer, M. A.; Gilbert, J. R.; Haines, J. L.; Pericak-Vance, M. A. Genome-wide association study implicates a chromosome 12 risk locus for late-onset Alzheimer disease. Am. J. Hum. Genet., 2009, 84, 35-43.
78. Thal, D. R.; Griffin, W. S.; de Vos, R. A.; Ghebremedhin, E. Cerebral amyloid angiopathy and its relationship to Alzheimer's disease. Acta Neuropathol., 2008, 115, 599-609.
79. Chalmers, K.; Wilcock, G. K.; Love, S. APOE epsilon 4 influences the pathological phenotype of Alzheimer's disease by favouring cerebrovascular over parenchymal accumulation of A beta protein. Neuropathol. Appl. Neurobiol., 2003, 29, 231-238.
80. Profenno, L. A.; Faraone, S. V. Diabetes and overweight associate with non-APOE4 genotype in an Alzheimer's disease population. Am. J. Med. Genet. B Neuropsychiatr. Genet., 2008, 147B, 822-829.
81. Messier, C. Diabetes, Alzheimer's disease and apolipoprotein genotype. Exp. Gerontol., 2003, 38, 941-946.
82. Musicco, M.; Palmer, K.; Salamone, G.; Lupo, F.; Perri, R.; Mosti, S.; Spalletta, G.; di, I. F.; Pettenati, C.; Cravello, L.; Caltagirone, C. Predictors of progression of cognitive decline in Alzheimer's disease: the role of vascular and sociodemographic factors. J. Neurol., 2009, 256, 1288-1295.
83. Xu, W.; Qiu, C.; Winblad, B.; Fratiglioni, L. The effect of borderline diabetes on the risk of dementia and Alzheimer's disease. Diabetes, 2007, 56, 211-216.
84. Xu, W. L.; Qiu, C. X.; Wahlin, A.; Winblad, B.; Fratiglioni, L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology, 2004, 63, 1181-1186.
85. Irie, F.; Fitzpatrick, A. L.; Lopez, O. L.; Kuller, L. H.; Peila, R.; Newman, A. B.; Launer, L. J. Enhanced risk for Alzheimer disease in persons with type 2 diabetes and APOE epsilon4: the Cardiovascular Health Study Cognition Study. Arch. Neurol., 2008, 65, 89-93.
86. Akomolafe, A.; Beiser, A.; Meigs, J. B.; Au, R.; Green, R. C.; Farrer, L. A.; Wolf, P. A.; Seshadri, S. Diabetes mellitus and risk of developing Alzheimer disease: results from the Framingham Study. Arch. Neurol., 2006, 63, 1551-1555.
87. Luchsinger, J. A.; Tang, M. X.; Shea, S.; Mayeux, R. Hyperinsulinemia and risk of Alzheimer disease. Neurology, 2004, 63, 1187 1192.
88. Whitmer, R. A.; Karter, A. J.; Yaffe, K.; Quesenberry, C. P., Jr.; Selby, J. V. Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus. JAMA, 2009, 301, 1565-1572.
89. Ott, A.; Stolk, R. P.; van, H. F.; Pols, H. A.; Hofman, A.; Breteler, M. M. Diabetes mellitus and the risk of dementia: The Rotterdam Study. Neurology, 1999, 53, 1937-1942.
90. Stolk, R. P.; Breteler, M. M.; Ott, A.; Pols, H. A.; Lamberts, S. W.; Grobbee, D. E.; Hofman, A. Insulin and cognitive function in an elderly population. The Rotterdam Study. Diabetes Care, 1997, 20, 792-795.
91. Biessels, G. J.; Staekenborg, S.; Brunner, E.; Brayne, C.; Scheltens, P. Risk of dementia in diabetes mellitus: a systematic review. Lancet Neurol., 2006, 5, 64-74.
92. Maher, P. A.; Schubert, D. R. Metabolic links between diabetes and Alzheimer's disease. Expert. Rev. Neurother., 2009, 9, 617-630.
93. Taguchi, A. Vascular factors in diabetes and Alzheimer's disease. J. Alzheimers. Dis., 2009, 16, 859-864.
94. in't Veld, B. A.; Ruitenberg, A.; Hofman, A.; Stricker, B. H.; Breteler, M. M. Antihypertensive drugs and incidence of dementia: the Rotterdam Study. Neurobiol. Aging, 2001, 22, 407-412.
95. Takeuchi, M.; Yamagishi, S. Possible involvement of advanced glycation end-products (AGEs) in the pathogenesis of Alzheimer's disease. Curr. Pharm. Des., 2008, 14, 973-978.
96. Yan, S. D.; Chen, X.; Fu, J.; Chen, M.; Zhu, H.; Roher, A.; Slattery, T.; Zhao, L.; Nagashima, M.; Morser, J.; Migheli, A.; Nawroth, P.; Stern, D.; Schmidt, A. M. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature, 1996, 382, 685-691.
97. Sugaya, K.; Fukagawa, T.; Matsumoto, K.; Mita, K.; Takahashi, E.; Ando, A.; Inoko, H.; Ikemura, T. Three genes in the human MHC class III region near the junction with the class II: gene for receptor of advanced glycosylation end products, PBX2 homeobox gene and a notch homolog, human counterpart of mouse mammary tumor gene int-3. Genomics, 1994, 23, 408-419.
98. Naka, Y.; Bucciarelli, L. G.; Wendt, T.; Lee, L. K.; Rong, L. L.; Ramasamy, R.; Yan, S. F.; Schmidt, A. M. RAGE axis: Animal models and novel insights into the vascular complications of diabetes. Arterioscler. Thromb. Vasc. Biol., 2004, 24, 1342-1349.
99. Bucciarelli, L. G.; Wendt, T.; Rong, L.; Lalla, E.; Hofmann, M. A.; Goova, M. T.; Taguchi, A.; Yan, S. F.; Yan, S. D.; Stern, D. M.; Schmidt, A. M. RAGE is a multiligand receptor of the immunoglobulin superfamily: implications for homeostasis and chronic disease. Cell Mol. Life Sci., 2002, 59, 1117-1128.
100. Lue, L. F.; Walker, D. G.; Jacobson, S.; Sabbagh, M. Receptor for advanced glycation end products: its role in Alzheimer's disease and other neurological diseases. Future. Neurol., 2009, 4, 167-177.
101. Lue, L. F.; Yan, S. D.; Stern, D. M.; Walker, D. G. Preventing activation of receptor for advanced glycation endproducts in Alzheimer's disease. Curr. Drug Targets. CNS. Neurol. Disord., 2005, 4, 249-266.
102. Yamagishi, S.; Nakamura, K.; Matsui, T.; Ueda, S.; Fukami, K.; Okuda, S. Agents that block advanced glycation end product (AGE)-RAGE (receptor for AGEs)-oxidative stress system: a novel therapeutic strategy for diabetic vascular complications. Expert. Opin. Investig. Drugs, 2008, 17, 983-996.
103. Huijberts, M. S.; Schaper, N. C.; Schalkwijk, C. G. Advanced glycation end products and diabetic foot disease. Diabetes Metab Res. Rev., 2008, 24(Suppl 1), S19-S24.
104. Jandeleit-Dahm, K.; Watson, A.; Soro-Paavonen, A. The AGE/RAGE axis in diabetes-accelerated atherosclerosis. Clin. Exp. Pharmacol. Physiol, 2008, 35, 329-334.
105. Yamagishi, S.; Nakamura, K.; Imaizumi, T. Advanced glycation end products (AGEs) and diabetic vascular complications. Curr. Diabetes Rev., 2005, 1, 93-106.
106. Yan, S. F.; Naka, Y.; Hudson, B. I.; Herold, K.; Yan, S. D.; Ramasamy, R.; Schmidt, A. M. The ligand/RAGE axis: lighting the fuse and igniting vascular stress. Curr. Atheroscler. Rep., 2006, 8, 232-239.
107. Hudson, B. I.; Wendt, T.; Bucciarelli, L. G.; Rong, L. L.; Naka, Y.; Yan, S. F.; Schmidt, A. M. Diabetic vascular disease: it's all the RAGE. Antioxid. Redox. Signal., 2005, 7, 1588-1600.
108. Sato, T.; Shimogaito, N.; Wu, X.; Kikuchi, S.; Yamagishi, S.; Takeuchi, M. Toxic advanced glycation end products (TAGE) theory in Alzheimer's disease. Am. J. Alzheimers. Dis. Other Demen., 2006, 21, 197-208.
109. Sato, T.; Iwaki, M.; Shimogaito, N.; Wu, X.; Yamagishi, S.; Takeuchi, M. TAGE (toxic AGEs) theory in diabetic complications. Curr. Mol. Med., 2006, 6, 351-358.
110. Takeuchi, M.; Yamagishi, S. Involvement of toxic AGEs (TAGE) in the pathogenesis of diabetic vascular complications and Alzheimer's disease. J. Alzheimers. Dis., 2009, 16, 845-858.
111. Donahue, J. E.; Flaherty, S. L.; Johanson, C. E.; Duncan, J. A., III; Silverberg, G. D.; Miller, M. C.; Tavares, R.; Yang, W.; Wu, Q.; Sabo, E.; Hovanesian, V.; Stopa, E. G. RAGE, LRP-1, and amyloid beta protein in Alzheimer's disease. Acta Neuropathol., 2006, 112, 405-415.
112. Jeynes, B.; Provias, J. Evidence for altered LRP/RAGE expression in Alzheimer lesion pathogenesis. Curr. Alzheimer Res., 2008, 5, 432-437.
113. Miller, M. C.; Tavares, R.; Johanson, C. E.; Hovanesian, V.; Donahue, J. E.; Gonzalez, L.; Silverberg, G. D.; Stopa, E. G. Hippocampal RAGE immunoreactivity in early and advanced Alzheimer's disease. Brain Res., 2008, 1230, 273-280.
114. Sasaki, N.; Toki, S.; Chowei, H.; Saito, T.; Nakano, N.; Hayashi, Y.; Takeuchi, M.; Makita, Z. Immunohistochemical distribution of the receptor for advanced glycation end products in neurons and astrocytes in Alzheimer's disease. Brain Res., 2001, 888, 256-262.
115. Deane, R.; Bell, R. D.; Sagare, A.; Zlokovic, B. V. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol. Disord. Drug Targets., 2009, 8, 16-30.
116. Giri, R.; Selvaraj, S.; Miller, C. A.; Hofman, F.; Yan, S. D.; Stern, D.; Zlokovic, B. V.; Kalra, V. K. Effect of endothelial cell polarity on beta-amyloid-induced migration of monocytes across normal and AD endothelium. Am. J. Physiol. Cell Physiol., 2002, 283, C895-C904.
117. Verdier, Y.; Zarandi, M.; Penke, B. Amyloid beta-peptide interactions with neuronal and glial cell plasma membrane: binding sites and implications for Alzheimer's disease. J. Pept. Sci., 2004, 10, 229-248.
118. Verdier, Y.; Penke, B. Binding sites of amyloid beta-peptide in cell plasma membrane and implications for Alzheimer's disease. Curr. Protein Pept. Sci., 2004, 5, 19-31.
119. Xie, L.; Helmerhorst, E.; Taddei, K.; Plewright, B.; Van, B. W.; Martins, R. Alzheimer's beta-amyloid peptides compete for insulin binding to the insulin receptor. J. Neurosci., 2002, 22, RC221.
120. Liao, F. F.; Xu, H. Insulin signaling in sporadic Alzheimer's disease. Sci. Signal., 2009, 2, e36.
121. Zhao, W. Q.; De Felice, F. G.; Fernandez, S.; Chen, H.; Lambert, M. P.; Quon, M. J.; Krafft, G. A.; Klein, W. L. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FASEB J., 2008, 22, 246-260.
122. De Felice, F. G.; Vieira, M. N.; Bomfim, T. R.; Decker, H.; Velasco, P. T.; Lambert, M. P.; Viola, K. L.; Zhao, W. Q.; Ferreira, S. T.; Klein, W. L. Protection of synapses against Alzheimer's-linked toxins: insulin signaling prevents the pathogenic binding of Abeta oligomers. Proc. Natl. Acad. Sci. USA, 2009, 106, 1971-1976.
123. Qiu, W. Q.; Walsh, D. M.; Ye, Z.; Vekrellis, K.; Zhang, J.; Podlisny, M. B.; Rosner, M. R.; Safavi, A.; Hersh, L. B.; Selkoe, D. J. Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J. Biol. Chem., 1998, 273, 32730-32738.
124. McDermott, J. R.; Gibson, A. M. Degradation of Alzheimer's betaamyloid protein by human and rat brain peptidases: involvement of insulin-degrading enzyme. Neurochem. Res., 1997, 22, 49-56.
125. Kurochkin, I. V.; Goto, S. Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett., 1994, 345, 33-37.
126. Farris, W.; Mansourian, S.; Chang, Y.; Lindsley, L.; Eckman, E. A.; Frosch, M. P.; Eckman, C. B.; Tanzi, R. E.; Selkoe, D. J.; Guenette, S. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. USA, 2003, 100, 4162-4167.
127. Vekrellis, K.; Ye, Z.; Qiu, W. Q.; Walsh, D.; Hartley, D.; Chesneau, V.; Rosner, M. R.; Selkoe, D. J. Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulindegrading enzyme. J. Neurosci., 2000, 20, 1657-1665.
128. Farris, W.; Mansourian, S.; Leissring, M. A.; Eckman, E. A.; Bertram, L.; Eckman, C. B.; Tanzi, R. E.; Selkoe, D. J. Partial lossof function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. Am. J. Pathol., 2004, 164, 1425-1434.
129. Fernandez-Gamba, A.; Leal, M. C.; Morelli, L.; Castano, E. M. Insulin-degrading enzyme: structure-function relationship and its possible roles in health and disease. Curr. Pharm. Des., 2009, 15, 3644-3655.
130. Qiu, W. Q.; Folstein, M. F. Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer's disease: review and hypothesis. Neurobiol. Aging, 2006, 27, 190-198.
131. Ho, L.; Qin, W.; Pompl, P. N.; Xiang, Z.; Wang, J.; Zhao, Z.; Peng, Y.; Cambareri, G.; Rocher, A.; Mobbs, C. V.; Hof, P. R.; Pasinetti, G. M. Diet-induced insulin resistance promotes amyloidosis in a transgenic mouse model of Alzheimer's disease. FASEB J., 2004, 18, 902-904.
132. Zhao, L.; Teter, B.; Morihara, T.; Lim, G. P.; Ambegaokar, S. S.; Ubeda, O. J.; Frautschy, S. A.; Cole, G. M. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J. Neurosci., 2004, 24, 11120-11126.
133. Caccamo, A.; Oddo, S.; Sugarman, M. C.; Akbari, Y.; LaFerla, F. M. Age and region-dependent alterations in Abeta-degrading enzymes: implications for Abeta-induced disorders. Neurobiol. Aging, 2005, 26, 645-654.
134. Imrie, H.; Abbas, A.; Kearney, M. Insulin resistance, lipotoxicity and endothelial dysfunction. Biochim. Biophys. Acta, 2010, 1801, 320-326.
135. Belfiore, A.; Frasca, F.; Pandini, G.; Sciacca, L.; Vigneri, R. Insulin receptor isoforms and insulin receptor/insulin-like growth factor receptor hybrids in physiology and disease. Endocr. Rev., 2009, 30, 586-623.
136. Staiger, H.; Machicao, F.; Fritsche, A.; Haring, H. U. Pathomechanisms of type 2 diabetes genes. Endocr. Rev., 2009, 30, 557-585.
137. Fernandez-Veledo, S.; Nieto-Vazquez, I.; Vila-Bedmar, R.; Garcia Guerra, L.; onso-Chamorro, M.; Lorenzo, M. Molecular mechanisms involved in obesity-associated insulin resistance: therapeutical approach. Arch. Physiol. Biochem., 2009, 115, 227-239.
138. Venables, M. C.; Jeukendrup, A. E. Physical inactivity and obesity: links with insulin resistance and type 2 diabetes mellitus. Diabetes Metab Res. Rev., 2009, 25(Suppl 1), S18-S23.
139. McIntyre, R. S.; Vagic, D.; Swartz, S. A.; Soczynska, J. K.; Woldeyohannes, H. O.; Voruganti, L. P.; Konarski, J. Z. Insulin, insulin-like growth factors and incretins: neural homeostatic regulators and treatment opportunities. CNS Drugs, 2008, 22, 443-453.
140. Craft, S.; Peskind, E.; Schwartz, M. W.; Schellenberg, G. D.; Raskind, M.; Porte, D., Jr. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology, 1998, 50, 164-168.
141. Watson, G. S.; Craft, S. Insulin resistance, inflammation, and cognition in Alzheimer's Disease: lessons for multiple sclerosis. J. Neurol. Sci., 2006, 245, 21-33.
142. Krogh-Madsen, R.; Plomgaard, P.; Keller, P.; Keller, C.; Pedersen, B. K. Insulin stimulates interleukin-6 and tumor necrosis factoralpha gene expression in human subcutaneous adipose tissue. Am. J. Physiol. Endocrinol. Metab., 2004, 286, E234-E238.
143. Krogh-Madsen, R.; Moller, K.; Dela, F.; Kronborg, G.; Jauffred, S.; Pedersen, B. K. Effect of hyperglycemia and hyperinsulinemia on the response of IL-6, TNF-alpha, and FFAs to low-dose endotoxemia in humans. Am. J. Physiol. Endocrinol. Metab., 2004, 286, E766-E772.
144. Soop, M.; Duxbury, H.; Agwunobi, A. O.; Gibson, J. M.; Hopkins, S. J.; Childs, C.; Cooper, R. G.; Maycock, P.; Little, R. A.; Carlson, G. L. Euglycemic hyperinsulinemia augments the cytokine and endocrine responses to endotoxin in humans. Am. J. Physiol. Endocrinol. Metab, 2002, 282, E1276-E1285.
145. Magistretti, P. J.; Pellerin, L. Cellular mechanisms of brain energy metabolism. Relevance to functional brain imaging and to neurodegenerative disorders. Ann. N. Y. Acad. Sci., 1996, 777, 380-387.
146. Feil, D. G.; Pearman, A.; Victor, T.; Harwood, D.; Weinreb, J.; Kahle, K.; Unutzer, J. The role of cognitive impairment and caregiver support in diabetes management of older outpatients. Int. J. Psychiatry Med., 2009, 39, 199-214.
147. Sommerfield, A. J.; Deary, I. J.; Frier, B. M. Acute hyperglycemia alters mood state and impairs cognitive performance in people with type 2 diabetes. Diabetes Care, 2004, 27, 2335-2340.
148. Yaffe, K.; Blackwell, T.; Whitmer, R. A.; Krueger, K.; Barrett, C. E. Glycosylated hemoglobin level and development of mild cognitive impairment or dementia in older women. J. Nutr. Health Aging, 2006, 10, 293-295.
149. Ryan, C. M.; Geckle, M. O. Circumscribed cognitive dysfunction in middle-aged adults with type 2 diabetes. Diabetes Care, 2000, 23, 1486-1493.
150. Szkudelski, T. The mechanism of alloxan and streptozotocin action in B cells of the rat pancreas. Physiol. Res., 2001, 50, 537-546.
151. Leal, M. C.; Dorfman, V. B.; Gamba, A. F.; Frangione, B.; Wisniewski, T.; Castano, E. M.; Sigurdsson, E. M.; Morelli, L. Plaque-associated overexpression of insulin-degrading enzyme in the cerebral cortex of aged transgenic tg2576 mice with Alzheimer pathology. J. Neuropathol. Exp. Neurol., 2006, 65, 976-987.
152. Vepsalainen, S.; Hiltunen, M.; Helisalmi, S.; Wang, J.; van, G. T.; Tanila, H.; Soininen, H. Increased expression of Abeta degrading enzyme IDE in the cortex of transgenic mice with Alzheimer's disease like neuropathology. Neurosci. Lett., 2008, 438, 216-220.
153. Jolivalt, C. G.; Lee, C. A.; Beiswenger, K. K.; Smith, J. L.; Orlov, M.; Torrance, M. A.; Masliah, E. Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer's disease and correction by insulin. J. Neurosci. Res., 2008, 86, 3265-3274.
154. Takeda, S.; Sato, N.; Uchio-Yamada, K.; Sawada, K.; Kunieda, T.; Takeuchi, D.; Kurinami, H.; Shinohara, M.; Rakugi, H.; Morishita, R. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc. Natl. Acad. Sci. USA, 2010, 107, 7036-7041.
155. Plaschke, K.; Kopitz, J.; Siegelin, M.; Schliebs, R.; Salkovic Petrisic, M.; Riederer, P.; Hoyer, S. Insulin-resistant brain state after intracerebroventricular streptozotocin injection exacerbates Alzheimer-like changes in Tg2576 AbetaPP-overexpressing mice. J. Alzheimers Dis., 2010, 19, 691-704.
156. Jolivalt, C. G.; Hurford, R.; Lee, C. A.; Dumaop, W.; Rockenstein, E.; Masliah, E. Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice. Exp. Neurol., 2010, 223, 422-431.
157. Ke, Y. D.; Delerue, F.; Gladbach, A.; Gotz, J.; Ittner, L. M. Experimental diabetes mellitus exacerbates tau pathology in a transgenic mouse model of Alzheimer's disease. PLoS One, 2009, 4, e7917.
158. Plastino, M.; Fava, A.; Pirritano, D.; Cotronei, P.; Sacco, N.; Sperli, T.; Spano, A.; Gallo, D.; Mungari, P.; Consoli, D.; Bosco, D. Effects of insulinic therapy on cognitive impairment in patients with Alzheimer disease and diabetes mellitus type-2. J. Neurol. Sci., 2010, 288, 112-116.
159. Sanz, C.; Andrieu, S.; Sinclair, A.; Hanaire, H.; Vellas, B. Diabetes is associated with a slower rate of cognitive decline in Alzheimer disease. Neurology, 2009, 73, 1359-1366.
160. Heneka, M. T.; Landreth, G. E. PPARs in the brain. Biochim. Biophys. Acta, 2007, 1771, 1031-1045.
161. Sundararajan, S.; Jiang, Q.; Heneka, M.; Landreth, G. PPARgamma as a therapeutic target in central nervous system diseases. Neurochem. Int., 2006, 49, 136-144.
162. Hanyu, H.; Sato, T.; Kiuchi, A.; Sakurai, H.; Iwamoto, T. Pioglitazone improved cognition in a pilot study on patients with Alzheimer's disease and mild cognitive impairment with diabetes mellitus. J. Am. Geriatr. Soc., 2009, 57, 177-179.
163. Heneka, M. T.; Sastre, M.; Dumitrescu-Ozimek, L.; Hanke, A.; Dewachter, I.; Kuiperi, C.; O'Banion, K.; Klockgether, T.; Van, L. F.; Landreth, G. E. Acute treatment with the PPARgamma agonist pioglitazone and ibuprofen reduces glial inflammation and Abeta1 42 levels in APPV717I transgenic mice. Brain, 2005, 128, 1442-1453.
164. Nicolakakis, N.; Aboulkassim, T.; Ongali, B.; Lecrux, C.; Fernandes, P.; Rosa-Neto, P.; Tong, X. K.; Hamel, E. Complete rescue of cerebrovascular function in aged Alzheimer's disease transgenic mice by antioxidants and pioglitazone, a peroxisome proliferatoractivated receptor gamma agonist. J. Neurosci., 2008, 28, 9287 9296.
165. Sato, T.; Hanyu, H.; Hirao, K.; Kanetaka, H.; Sakurai, H.; Iwamoto, T. Efficacy of PPAR-gamma agonist pioglitazone in mild Alzheimer disease. Neurobiol. Aging, 2009 [Epub ahead of print].
166. Pedersen, W. A.; McMillan, P. J.; Kulstad, J. J.; Leverenz, J. B.; Craft, S.; Haynatzki, G. R. Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp. Neurol., 2006, 199, 265-273.
167. Risner, M. E.; Saunders, A. M.; Altman, J. F.; Ormandy, G. C.; Craft, S.; Foley, I. M.; Zvartau-Hind, M. E.; Hosford, D. A.; Roses, A. D. Efficacy of rosiglitazone in a genetically defined population with mild-to-moderate Alzheimer's disease. Pharmacogenom. J., 2006, 6, 246-254.
168. Banks, W. A. The source of cerebral insulin. Eur. J. Pharmacol., 2004, 490, 5-12.
169. Kodl, C. T.; Seaquist, E. R. Cognitive dysfunction and diabetes mellitus. Endocr. Rev., 2008, 29, 494-511.