Glucose metabolism and insulin receptor signal transduction in Alzheimer disease

European Journal of Pharmacology

Volumn 490, Issue 1-3, 2004, Pages 115-125

  Hoyer, Siegfried ^a  

^a UNIVERSITY OF HEIDELBERG   (Germany)

Author keywords

Alzheimer disease; Brain; Glucose; Glucose energy metabolism; Insulin; Insulin receptor

Indexed keywords

ADENOSINE TRIPHOSPHATE; AMYLOID BETA PROTEIN; AMYLOID PRECURSOR PROTEIN; GLUCOSE; INSULIN RECEPTOR; TAU PROTEIN;

AGING; ALZHEIMER DISEASE; ARTICLE; BINDING AFFINITY; BRAIN NERVE CELL; CELL DAMAGE; ENERGY METABOLISM; FAMILIAL DISEASE; GENE MUTATION; GENETIC ANALYSIS; GENETIC SUSCEPTIBILITY; GLUCOSE METABOLISM; HUMAN; INHIBITION KINETICS; INSULIN SYNTHESIS; NERVE CELL; NERVE CONDUCTION; NONHUMAN; OXIDATION; PATHOPHYSIOLOGY; PHENOTYPE; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN BINDING; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN METABOLISM; PROTEIN PHOSPHORYLATION; REGULATORY MECHANISM; RISK ASSESSMENT; RISK FACTOR; SENESCENCE; SIGNAL TRANSDUCTION;

AGE OF ONSET; ALZHEIMER DISEASE; ANIMALS; GLUCOSE; HUMANS; INSULIN; MODELS, BIOLOGICAL; RECEPTOR, INSULIN; SIGNAL TRANSDUCTION;

EID: 1842785179     PISSN: 00142999     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.ejphar.2004.02.049     Document Type: Article

References (148)

1. Adamo M., Raizada M.K., Le Roith D. Insulin and insulin-like growth factor receptors in the nervous system. Mol. Neurobiol. 3:1989;71-100.
2. Alessi D.R., Cohen P. Mechanism of activation and function of protein kinase B. Curr. Opin. Genet. Dev. 8:1998;55-62.
3. Arias C., Montiel T., Quiroz-Baez R., Massieu L. β-Amyloid neurotoxicity is exacerbated during glycolysis inhibition and mitochondrial impairment in the rat hippocampus in vivo and in isolated nerve terminals: implications for Alzheimer's disease. Exp. Neurol. 176:2002;163-174.
4. Bak P., Tang C., Wiesenfeld K. Self-organized criticality. Phys. Rev., A. 38:1988;365-374.
5. Balbo S.L., Bonfleur M.L., Carneiro E.M., Amaral M.E.C.D., Filiputti E., Mathias P.C.F. Parasympathic activity changes insulin response to glucose and neurotransmitters. Diabetes Metab. 28:2002;3S13-3S17.
6. Baskin D.G., Schwartz M.W., Sipols A.J., D'Alessio D.A., Goldstein B.J., White M.F. Insulin receptor substrate-I (IRS-I) expression in rat brain. Endocrinology. 134:1994;1952-1955.
7. Baskin D.S., Browning J.L., Pirozzolo F.J., Korporaal S., Baskin J.A., Appel S.H. Brain choline acetyltransferase and mental function in Alzheimer disease. Arch. Neurol. 56:1999;1221-1223.
8. Bernstein H.G., Ansorge S., Riederer P., Reiser F.M., Frölich L., Bogerts B. Insulin-degrading enzyme in Alzheimer's disease brain: prominent localization in neurons and senile plaques. Neurosci. Lett. 263:1999;161-164.
9. Bigl M., Bleyl A.D., Zedlick D., Arendt T., Bigl V., Eschrich K. Changes of activity and isoenzyme pattern of phosphofructokinase in the brains of patients with Alzheimer's disease. J. Neurochem. 67:1996;1164-1171.
10. Bigl M., Brückner M.K., Arendt T., Bigl V., Eschrich K. Activities of key glycolytic enzymes in the brains of patients with Alzheimer's disease. J. Neural Transm. 106:1999;499-511.
11. Bigl M., Beck M., Bleyl A.D., Bigl V., Eschrich K. Altered phosphofructokinase mRNA levels but unchanged isoenzyme pattern in brains from patients with Alzheimer's disease. Mol. Brain Res. 76:2000;411-414.
12. Bigl M., Apelt J., Eschrich K., Schliebs R. Cortical glucose metabolism is altered in aged transgenic Tg 2576 mice that demonstrate Alzheimer plaque pathology. J. Neural Transm. 110:2003;77-94.
13. 31P-NMR profiles of Alzheimer disease and multiple subcortical infarct dementia. Neurology. 39:1989;1423-1427.
14. Bucht G., Adolfsson R., Lithner F., Winblad B. Changes in blood glucose and insulin secretion in patients with senile dementia of Alzheimer type. Acta Med. Scand. 213:1983;387-392.
15. Buttgereit F., Brand M.D. A hierarchy of ATP-consuming processes in mammalian cells. Biochem. J. 312:1995;163-167.
16. Cho K.S., Choi J., Ha C.M., Son Y.J., Choi W.S., Lee B.K. Comparison of gene expression in old versus young rat hippocampus by cDNA array. NeuroReport. 13:2002;285-289.
17. Chou C.K., Dull T.J., Russel D.S., Gherzi R., Lebwohl D., Ullrich A., Rosen O.M. Human insulin receptors mutated at the ATP-binding site lack protein tyrosine kinase activity and fail to mediate postreceptor effects of insulin. J. Biol. Chem. 262:1987;1842-1847.
18. Cizza G., Calogero A.E., Brady L.S., Bagdy G., Bergamini E., Blackman M.R., Chrousos G.P., Gold P.W. Male Fischer 344/N rats show a progressive central impairment of the hypothalamic-pituitary-adrenal axis with advancing age. Endocrinology. 134:1994;1611-1620.
19. Cook D.G., Forman F.S., Sung I.C., Leight S., Kolson D.L., Iwatsubo T., Lee V.M.Y., Doms R.W. Alzheimer's Aβ (1-42) is generated in the endoplasmic reticulum/intermediate compartment of NT2N cells. Nat. Med. 3:1997;1021-1023.
20. Cook D.G., Leverenz J.B., McMillan P.J., Kulstadt J.J., Ericksen S., Roth R.A., Schellenberg G.D., Jin L.W., Kovacina K.S., Craft S. Reduced hippocampal insulin degrading enzyme in late onset Alzheimer's disease is associated with the apolipoprotein E-ε 4 allele. Am. J. Pathol. 162:2003;313-319.
21. 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. 50:1998;164-168.
22. Craft S., Asthana S., Schellenberg G., Cherrier M., Baker L.D., Newcomer J., Plymate S., Latendresse S., Petrova A., Raskind M., Peskind E., Lofgreen C., Grimwood K. Insulin metabolism in Alzheimer's disease differs according to apolipoprotein E genotype and gender. Neuroendocrinology. 70:1999;146-152.
23. Craft S., Peskind E., Asthana S., Watson G.S., Baker L.D., Cook D.G., Schwartz M.W. Effects of insulin on cerebrospinal levels of Aβ42. Neurobiol. Aging. 21:2000;S272. (1245).
24. Cross D.A.E., Alessi D.R., Cohen P., Andjelkovich M., Hemmings B.A. Inhibition of glycogen synthase kinase-3 by insulin mediated protein kinase. Nature. 378:1995;785-789.
25. Cross D.A., Watt P.W., Shaw M., von der Kaay J., Downes C.P., Holder J.C., Cohen P. Insulin activates protein kinase B, inhibits glycogen synthase kinase-3 and activates glycogen synthase by rapamycin-sensitive pathways in skeletal muscle and adipose tissue. FEBS Lett. 406:1997;211-215.
26. D'Andrea M.R., Nagele R.G., Wang H.Y., Peterson P.A., Lee D.H.S. Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease. Histopathology. 38:2001;120-134.
27. Devaskar S.U., Giddings S.J., Rajakumar P.A., Carnaghi L.R., Menon R.K., Zahn D.S. Insulin gene expression and insulin synthesis in mammalian neuronal cells. J. Biol. Chem. 269:1994;8445-8454.
28. Dorner A.J., Wasley L.C., Kaufman R.J. Protein dissociation from GRP 78 and secretion are blocked by depletion of cellular ATP levels. Proc. Natl. Acad. Sci. U. S. A. 87:1990;7429-7432.
29. Duara R., Grady C., Haxby J., Sundaram S., Cutler N.R., Heston L., Moore A., Schlageter N., Larson S., Rapoport S.I. Positron emission tomography in Alzheimer's disease. Neurology. 36:1986;879-887.
30. Duckworth W.C. Insulin degradation: mechanisms, products, and significance. Endocr. Rev. 9:1988;319-345.
31. Duelli R., Schröck H., Kuschinsky W., Hoyer S. Intracerebroventricular injection of streptozotocin induces discrete local changes in cerebral glucose utilization in rats. Int. J. Dev. Neurosci. 12:1994;737-743.
32. Eckert G.P., Cairns N.J., Maras A., Gattaz W.F., Müller W.E. Cholesterol modulates the membrane-disordering effects of beta-amyloid peptides in the hippocampus: specific changes in Alzheimer's disease. Dement. Geriatr. Cogn. Disord. 11:2000;181-186.
33. Erecinska M., Silver I.A. ATP and brain function. J. Cereb. Blood Flow Metab. 9:1989;2-19.
34. Farris W., Mansourian S., Chang Y., Lindsay L., Eckman E.A., Frosch M.P., Eckman C.B., Tanzi R.E., Selkoe D.E., Guenette S. Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo. Proc. Natl. Acad. Sci. U. S. A. 100:2003;4162-4167.
35. Foster N.L., Chase T.N., Mansi L., Brooks R., Fedio P., Patronas N.J., DiChiro G. Cortical abnormalities in Alzheimer's disease. Ann. Neurol. 16:1984;649-654.
36. Frölich L., Blum-Degen D., Bernstein H.G., Engelsberger S., Humrich J., Laufer S.et al. Insulin and insulin receptors in the brain in aging and sporadic Alzheimer's disease. J. Neural Transm. 105:1998;423-438.
37. Fukuyama H., Ogawa M., Yamauchi H., Yamaguchi S., Kimura J., Yonekura Y., Konishi J. Altered cerebral energy metabolism in Alzheimer's disease: a PET study. J. Nucl. Med. 35:1994;1-6.
38. Gasparini L., Gouras G.K., Wang R., Gross R.S., Beal M.F., Greengard P., Xu H. Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneuronal β-amyloid and requires mitogen-activated protein kinase signaling. J. Neurosci. 21:2001;2561-2570.
39. Ghidoni R., Gasparini L., Alberici A., Benussi L., Barbiero L., Mazzoli F., Nicosia F., Finazzi D., Benerini Gatta L., Albertini A., Zanetti O., Binetti G. Inhibition of energy metabolism down-regulates the Alzheimer related presenilin 2 gene. J. Neural Transm. 110:2003;1029-1039.
40. Gibson G.E., Jope R., Blass J.P. Decreased synthesis of acetylcholine accompanying impaired oxidation of pyruvic acid in rat brain minces. Biochem. J. 148:1975;17-23.
41. Giorgino F., Almahfouz A., Goodyear L.J., Smith R.J. Glucocorticoid regulation of insulin receptor and substrate IRS-1 tyrosine phosphorylation in rat skeletal muscle in vivo. J. Clin. Invest. 91:1993;2020-2030.
42. Goldstein B.J. Regulation of insulin receptor signalling by protein-tyrosine dephosphorylation. Receptor. 3:1993;1-5.
43. Gong C.X., Grundke-Iqbal I., Iqbal K. Dephosphorylation of Alzheimer disease abnormally phosphorylated tau: decrease in Alzheimer disease. Diabetologica. 61:1994;765-772.
44. Gouras G.K., Tsai J., Naslund J., Vincent B., Edgard M., Greenfield J.P., Haroutunian V., Buxbaum J.S., Xu H., Greengard P., Relkin N.R. Intraneuronal βA42 accumulation in human brain. Am. J. Pathol. 156:2000;15-20.
45. Greenfield J.P., Tsai J., Gouras G.K., Hai B., Thinakaran G., Checter F., Sisodia S.S., Greengard P., Xu H. Endoplasmic reticulum and trans-Golgi network generate distinct populations of Alzheimer β-amyloid peptides. Proc. Natl. Acad. Sci. U. S. A. 96:1999;742-747.
46. Häring H.U. The insulin receptor: signalling mechanism and contribition to the pathogenesis of insulin resistance. Diabetologica. 34:1991;848-861.
47. Häring H.U., Kirsch D., Obermaier B., Ermel B., Machicao F. Decreased tyrosine kinase activity of insulin receptor isolated from rat adipocytes rendered insulin-resistant by catecholamine treatment in vitro. Biochem. J. 234:1986;59-66.
48. Hardy J., Selkoe D.J. The amyloid hypothesis of Alzheimer's disease: progress and problems on the road of therapeutics. Science. 297:2002;353-356.
49. Hartmann T., Bieger S.C., Brühl B., Tienari P.J., Ida N., Allsop D., Roberts G.W., Masters C.L., Dotti C.G., Unsicker K., Beyreuther K. Distinct sites of intracelllular production for Alzheimer's disease Aβ 40/42 amyloid peptides. Nat. Med. 3:1997;1016-1020.
50. Heidenreich K.A., Zahniser N.R., Berhanu P., Brandenburg D., Olefsky J.M. Structural differences between insulin receptors in the brain and peripheral target tissues. J. Biol. Chem. 258:1983;8527-8530.
51. Held G.A., Solina D.H., Keane D.T., Haag W.J., Horn P.M., Grinstein G. Experimental study of critical mass fluctuations in an evolving sandpile. Phys. Rev. Lett. 69:1990;110-1123.
52. Hellweg R., Nitsch R., Hock C., Jaksch M., Hoyer S. Nerve growth factor and choline acetyltransferase activity levels in the rat brain following experimental impairment of cerebral glucose and energy metabolism. J. Neurosci. Res. 31:1992;479-486.
53. Henneberg N., Hoyer S. Short-term or long-term intracerebroventricular (ivc) infusion of insulin exhibits a discrete anabolic effect on cerebral energy metabolism in the rat. Neurosci. Lett. 175:1994;153-156.
54. Henneberg N., Hoyer S. Desensitization of the neuronal insulin receptor: a new approach in the etiopathogenesis of late-onset sporadic dementia of the Alzheimer type (SDAT)? Arch. Gerontol. Geriatr. 21:1995;63-74.
55. Herholz K., Salmon E., Perani D., Baron J.C., Holthoff V., Frölich L., Schönknecht P., Ito K., Mielke R., Kalbe E.et al. Discrimination between Alzheimer dementia and controls by automated analysis of multicenter FDG PET. NeuroImage. 17:2002;302-316.
56. Hess B. Non-equilibrium dynamics of biological processes. Hoppe-Seyler Z. Physiol. Chem. 364:1983;1-20.
57. Hess B. Order and chaos in chemistry and biology. Fresenius' J. Anal. Chem. 337:1990;459-468.
58. Hill J.M., Lesniak M.A., Pert C.B., Roth J. Autoradiographic localization of insulin receptors in rat brain: prominences in olfactory and limbic areas. Diabetologica. 17:1986;1128-1138.
59. Holness M.J., Langdown M.K., Sugden M.C. Early-life programming of susceptibility to dysregulation of glucose metabolism and the development of type 2 diabetes mellitus. Biochem. J. 349:2000;657-665.
60. Hong M.F., Lee V.M.Y. Insulin and insulin-like growth factor-1 regulate tau phosphorylation in cultured human neurons. J. Biol. Chem. 272:1997;19547-19553.
61. Hoyer S. Oxidative energy metabolism in Alzheimer brain. Studies in early-onset and late-onset cases. Mol. Chem. Neuropathol. 16:1992;207-224.
62. Hoyer S. Age-related changes in cerebral oxidative metabolism. Implications for drug therapy. Drugs Aging. 6:1995;210-218.
63. Hoyer S. Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J. Neural Transm. 105:1998;415-422.
64. Hoyer S. Brain glucose and energy metabolism abnormalities in sporadic Alzheimer disease. Causes and consequences: an update. Exp. Gerontol. 35:2000;1363-1372.
65. Hoyer S. The brain insulin signal transduction system and sporadic (type II) Alzheimer disease: an update. J. Neural Transm. 109:2000;341-360.
66. Hoyer S. The aging brain. Changes in the neuronal insulin/insulin receptor signal transduction cascade trigger late-onset sporadic Alzheimer disease (SAD). A mini-review. J. Neural Transm. 109:2000;991-1002.
67. Hoyer S., Nitsch R. Cerebral excess release of neurotransmitter amino acids subsequent to reduced glucose metabolism in early-onset dementia of Alzheimer type. J. Neural Transm. (Gen.Sect). 75:1989;227-232.
68. Hoyer S., Oesterreich K., Wagner O. Glucose metabolism as the site of the primary abnormality in early-onset dementia of Alzheimer type? J. Neurol. 235:1988;143-148.
69. Hoyer S., Nitsch R., Oesterreich K. Ammonia is endogenously generated in the brain in the presence of presumed and verified dementia of Alzheimer type. Neurosci. Lett. 117:1990;358-362.
70. Hoyer S., Nitsch R., Oesterreich K. Predominant abnormality in cerebral glucose utilization in late-onset dementia of the Alzheimer-type: a cross-sectional comparison against advanced late-onset dementia and incipient early-onset cases. J. Neural Transm. (PD-Sect.). 3:1991;1-14.
71. Hoyer S., Prem L., Sorbi S., Amaducci L. Stimulation of glycolytic key enzymes in cerebral cortex by insulin. NeuroReport. 4:1993;991-993.
72. Hung H.C., Tsai M.J., Wu H.C., Lee E.H. Age-dependent increase in C7-1 gene expression in rat frontal cortex. Mol. Brain Res. 75:2000;330-336.
73. Imaizumi K., Miyoshi K., Katayama T., Yoneda T., Taniguchi M., Kudo T., Tohyama M. The unfolded protein response and Alzheimer's disease. Biochim. Biophys. Acta. 1536:2001;85-96.
74. Ishiguro K., Takamatsu M., Tomizawa K., Omori A., Takahashi M., Arioka M., Uchida T., Imahori K. Tau protein kinase I converts normal tau protein into A68-like component of paired helical filaments. J. Biol. Chem. 267:1992;10897-10901.
75. Ishiguro K., Shiratsuchi A., Sato S., Omori A., Arioka M., Kobayashi S., Uchida T. Glycogen synthase kinase 3-beta is identical to tau protein kinase I generating several epitopes of paired helical filaments. FEBS Lett. 325:1993;167-172.
76. Jiang C.H., Tsien J.Z., Schultz P.G., Hu K. The effects of aging on gene expression in the hypothalamus and cortex of mice. Proc. Natl. Acad. Sci. U. S. A. 98:2001;1930-1934.
77. Joseph J., Shukitt-Hale B., Denisova N.A., Martin A., Perry G., Smith M.A. Copernicus revisited: amyloid beta in Alzheimer's disease. Neurobiol. Aging. 22:2001;131-146.
78. Kaufman R.J. Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev. 13:1999;1211-1233.
79. King J.A., Edwards E. Earyl stress and genetic influences on hypothalamic-pituitary-adrenal axis functioning in adulthood. Horm. Behav. 36:1999;79-85.
80. Kuo W.L., Montag A.G., Rosner M.R. Insulin-degrading enzyme is differentially expressed and developmentally regulated in various rat tissues. Endocrinology. 132:1993;604-611.
81. Kurochkin I.V., Goto S. Alzheimer's beta-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett. 345:1994;33-37.
82. Kyriakis J.M., Hausman R.E., Peterson S.W. Insulin stimulates choline acetyltransferase activity in cultured embryonic chicken retina neurons. Proc. Natl. Acad. Sci. U. S. A. 84:1987;7463-7467.
83. Lai J.C.K., Cooper A.J.L. Neurotoxicity of ammonia and fatty acids: differential inhibition of mitochondrial dehydrogenases by ammonia and fatty acids coenyme A derivatives. Neurochem. Res. 16:1991;795-803.
84. Lannert H., Hoyer S. Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav. Neurosci. 112:1998;1199-1208.
85. Leloup C., Arluison M., Lepetit N., Cartier N., Marfaing-Jallat P., Ferre P., Penicaud L. Glucose transporter 2 (GLUT2): expression in specific brain nuclei. Brain Res. 638:1994;221-226.
86. Leloup C., Orosco M., Serradas P., Nicolaidis S., Penicaud L. Specific inhibition of GLUT2 in arcuate nucleus by antisence oligonucleotides suppresses nervous control of insulin secretion. Mol. Brain Res. 57:1998;275-280.
87. Lesort M., Jope R.S., Johnson G.V.W. Insulin transiently increases tau phosphorylation: involvement of glycogen synthase kinase-3β and Fyn tyrosine kinase. J. Neurochem. 72:1999;576-584.
88. Lupien S., Lecors A., Lussier I., Schwartz G., Nair N., Meany M. Basal cortical levels and cognitive deficits in human aging. J. Neurosci. 14:1994;2893-2903.
89. Mandelkow E.M., Drewes G., Biernet J., Gustke N., Van Lint J., Vandenheede J.R., Mandelkow E. Glycogen synthase kinase-3 and the Alzheimer-like state of microtubule-associated protein tau. FEBS Lett. 314:1992;215-221.
90. Martinez M., Fernandez E., Frank A., Guaza C., de la Fuente M., Hernandez A. Increased cerebral spinal fluid cAMP levels in Alzheimer's disease. Brain Res. 846:1999;265-267.
91. Mastrogiacomo F., Bergeron C., Kish S.J. Brain α-ketoglutarate dehydrogenase complex activity in Alzheimer's disease. J. Neurochem. 61:1993;2007-2014.
92. McDermott J.R., Gibson A.M. Degradatation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: involvement of insulin-degrading enzyme. Neurochem. Res. 22:1997;49-56.
93. Merkel P., Khoury N., Bertolotto C., Perfetti R. Insulin and glucose regulate the expression of the DNA repair enzyme XPD. Mol. Cell. Endocrinol. 201:2003;75-85.
94. Michikawa M., Yanagisawa K. Inhibition of cholesterol production but not of nonsterol isoprenoid products induces neuronal cell death. J. Neurochem. 72:1999;2278-2285.
95. Mielke R., Herholz K., Grond M., Kessler J., Heiss W.D. Differences of regional cerebral glucose metabolism between presenile and senile dementia of Alzheimer type. Neurobiol. Aging. 13:1992;93-98.
96. Mirollo R.E., Strogatz S.H. Synchronization of pulse-coupled biological oscillators. SIAM J. Appl. Math. 50:1990;1645-1649.
97. Moss A.M., Unger J.W., Moxley R.T., Livinston J.N. Location of phosphotyrosine-containing proteins by immunocytochemistry in the rat forebrain corresponds to the distribution of the insulin receptor. Proc. Natl. Acad. Sci. U. S. A. 87:1990;4453-4457.
98. Mukherjee A., Song E., Kihiko-Ehmann M., Goodman J.P. Jr., St.Pyrek J., Estus S., Hersh L.B. Insulysin hydrolyzes amyloid β peptide to products that are neither neurotoxic nor deposit on amyloid plaques. J. Neurosci. 20:2000;8745-8749.
99. Mulder M., Ravid R., Swaab D.F., de Kloet E.R., Haasdijk E.D., Julk J., van der Boom J., Havekes L.M. Reduced levels of cholesterol, phospholipids, and fatty acids in cerebrospinial fluid of Alzheimer disease patients are not related to apolipoprotein E4. Alzheimer Dis. Assoc. Disord. 12:1998;198-203.
100. Nitsch R., Hoyer S. Local action of the diabetogenic drug, streptozotocin, on glucose and energy metabolism in rat brain cortex. Neurosci. Lett. 128:1991;199-202.
101. Nitsch R.M., Slack B.E., Wurtman R.J., Growdon J. Release of Alzheimer amyloid precursor derivates stimulated by activation of muscarinic acetylcholine receptors. Science. 258:1992;304-307.
102. Nitsch R.M., Blusztajn J.K., Pittas A.G., Slak B.E., Growdon J.A., Wurtman R.J. Evidence for a membrane defect in Alzheimer disease brain. Proc. Natl. Acad. Sci. U. S. A. 89:1992;1671-1675.
103. Parhad I.M., Scott J.N., Cellars L.A., Bains J.A., Krekoski C.A., Clark A.W. Axonal atrophy in aging is associated with a decline in neurofilament gene expression. J. Neurosci. Res. 41:1995;355-366.
104. Perez A., Morelli L., Cresto J.C., Castano E.M. Degradation of soluble amyloid β-peptides 1-40, 1-42, and the Dutch variant 1-40Q by insulin degrading enzyme from Alzheimer disease and control brain. Neurochem. Res. 25:2000;247-255.
105. Pericak-Vance M.A., Haines J.L. Genetic susceptibility to Alzheimer disease. Trends Genet. 11:1995;504-508.
106. Perry E.K., Perry R.H., Tomlinson B.E., Blessed G., Gibson P.H. Coenzyme A-acetylating enzymes in Alzheimer's disease: possible cholinergic "compartment" of pyruvate dehydrogenase. Neurosci. Lett. 18:1980;105-110.
107. Peskind E.R., Elrod R., Dobie D.J., Pascualy M., Petrie E., Jensen C., Brodkin K., Murray S., Veith R.C., Raskind M.A. Cerebrospinal fluid epinephrine in Alzheimer's disease and normal aging. Neuropsychopharmacology. 19:1998;465-471.
108. Petanceska S.S., Gandy S. The phosphatidylinositol 3-kinase inhibitor wortmannin alters the metabolism of the Alzheimer's amyloid precursor protein. J. Neurochem. 73:1999;2316-2320.
109. Pettegrew J.W., Klunk W.E., Kanal E., Panchalingam K., McClure R.J. Changes in brain membrane phospholipid and high-energy phosphate metabolism precede dementia. Neurobiol. Aging. 16:1995;973-975.
110. Phiel C.J., Wilson C.A., Lee V.M.Y., Klein P.S. GSK-3α regulates production of Alzheimer's disease amyloid-β peptides. Nature. 423:2003;435-439.
111. Plaschke K., Hoyer S. Action of the diabetogenic drug streptozotocin on glycolytic and glycogenolytic metabolism in adult rat brain cortex and hippocampus. Int. J. Dev. Neurosci. 11:1993;477-483.
112. Plata-Salaman C.R. Insulin in the cerebrospinal fluid. Neurosci. Biobehav. Rev. 15:1991;243-258.
113. Prickaerts J., Blokland A., Honig W., Meng F., Jolles F. Spatial discrimination learning and choline acetyltransferase activity in streptozotocin-treated rats: effects of chronic treatment with acetyl-L-carnitine. Brain Res. 674:1995;142-146.
114. Prigogini I. What is entropy? Naturwissenschaften. 76:1989;1-8.
115. Rinaudo M.T., Curto M., Bruno R., Marino C., Rossetti V., Mostert M. Evidence of an insulin generated pyruvate dehydrogenase stimulating factor in rat brain plasma membranes. Ital. J. Biochem. 19:1987;909-913.
116. Rocchi A., Pellegrini S., Siciliano G., Murri L. Causative and susceptibility genes for Alzheimer's disease: a review. Brain Res. Bull. 61:2003;1-24.
117. Röder H.M., Ingram V.M. Two novel kinases phosphorylate tau and the KSP site of heavy neurofilament subunits in high stoichiometric ratios. J. Neurosci. 11:1991;3325-3342.
118. Salehi A., Swaab D.F. Diminished neuronal metabolic activity in Alzheimer's disease. J. Neural Transm. 106:1999;955-986.
119. Salehi M., Hodgkin B.J., Merry B.J., Goyns M.H. Age-related changes in gene expression in the rat brain revealed by differential display. Experientia. 52:1996;888-891.
120. Sapolsky R.M., Krey L.C., McEwen B.S. The Neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr. Res. 7:1986;284-301.
121. Seksek O., Biwersi J., Verkman A.S. Direct measurement of trans-Golgi pH in living cells and regulation by second messengers. J. Biol. Chem. 270:1995;4967-4970.
122. Sims N.R., Bowen D.M., Allen S.J., Smith C.C.T., Neary D., Thomas D.J., Davison A.N. Presynaptic cholinergic dysfunction in patients with dementia. J. Neurochem. 40:1983;503-509.
123. 14C) glucose in vitro in human neocortex. J. Neurochem. 41:1983;1329-1334.
124. Solano D.C., Sironi M., Bonfini C., Solarte S.B., Govoni S., Racchi M. Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway. FASEB J. 14:2000;1015-1022.
125. Sorbi S., Bird E.D., Blass J.P. Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann. Neurol. 13:1983;72-78.
126. Sun F.F., Fleming W.E., Taylor B.M. Degradation of membrane phospholipids in the cultured human astroglial cell line UC-11MG during ATP depletion. Biochem. Pharmacol. 45:1993;1149-1155.
127. Svennerholm L., Gottfries C.G. Membrane lipids, selectively diminished in Alzheimer brains, suggest synapse loss as a primary event in early-onset form (type I) and demyelination in late-onset form (type II). J. Neurochem. 62:1994;1039-1047.
128. Swaab D.F., Raadsheer F.C., Endert E.F., Hofman M.A., Kamphorst W.C., Ravid R. Increases in cortisol levels in aging and Alzheimer's disease in post mortem cerebrospinal fluid. Neuroendocrinology. 6:1994;681-687.
129. Tilley L., Morgan K., Kalsheker N. Genetic risk factors in Alzheimer's disease. J. Clin. Pathol.: Mol. Pathol. 51:1998;293-304.
130. Unger J.W., Livinston J.N., Moss A.M. Insulin receptors in the central nervous system: localization, signalling mechanism and functional aspects. Prog. Neurobiol. 36:1991;343-362.
131. Vallée M., Maccari S., Dellu F., Simon H., Le Moal M., Mayo W. Long-term effects of prenatal stress and postnatal handling on age-related glucocorticoid secretion and cognitive performance: a longitudinal study in the rat. Eur. J. Neurosci. 11:1999;2906-2916.
132. Vanhaesebroeck A., Alessi D.R. The PIK3K-PDK1 connection: more than just a road to PKB. Biochem. J. 346:2000;561-576.
133. Vekrellis K., Ye Z., Qiu W.Q., Walsh D., Hartley D., Chesneau U., Rosner M.R., Selkoe D.J. Neurons regulate extracellular levels of amyloid β-protein via preteolysis by insulin-degrading enzyme. J. Neurosci. 20:2000;1657-1665.
134. Verde C., Pascale M.C., Martive G., Lotti L.V., Torrisi M.R., Helenius A., Bonatti S. Effect of ATP depletion and DTT on the transport of membrane proteins from the endoplasmic reticulum and the intermediate compartment to the Golgi complex. Eur. J. Cell Biol. 67:1995;267-274.
135. Wallace W.C., Akar C.A., Lyons W.E. Amyloid precursor protein potentiates the neurotrophic activity of NGF. Mol. Brain Res. 52:1997;201-212.
136. Wallace W.C., Akar C.A., Lyons W.E., Kole H.K., Egan J.E., Wolozin B. Amyloid precursor protein requires the insulin signaling pathway for neurotrophic activity. Mol. Brain Res. 52:1997;213-227.
137. Wang J.Z., Gong C.X., Zaidi T., Grundke-Iqbal I., Iqbal K. Dephosphorylation of Alzheimer paired helical filaments by protein phosphatase-2A and -2B. J. Biol. Chem. 270:1995;4854-4860.
138. Watanabe A., Hasegawa M., Suzuki T., Takio K., Morishima-Kawashima M., Titani K., Arai T., Kosik K.S., Ihara Y. In vivo phosphorylation sites in fetal and adult rat tau. J. Biol. Chem. 268:1993;25712-25717.
139. White M.F., Kahn C.R. The insulin signalling system. J. Biol. Chem. 269:1994;1-4.
140. Whittemore S.R., Ebendal T., Lärkfors L., Olson L., Seiger A., Strömberg I., Persson H. Development and regional expression of beta nerve growth factor messenger RNA and protein in the rat central nervous system. Proc. Natl. Acad. Sci. U. S. A. 83:1986;817-821.
141. Wild-Bode C., Yamazaki T., Capell A., Leimer U., Steiner H., Ihara Y., Haass C. Intracellular generation and accumulation of amyloid β-peptide terminating at amino acid-42. J. Biol. Chem. 272:1997;16085-16088.
142. Wozniak M., Rydzewski B., Baker S.P., Raizada M.K. The cellular and physiological actions of insulin in the central nervous system. Neurochem. Int. 22:1993;1-10.
143. Wu H.C., Lee E.H.Y. Indentification of a rat brain gene associated with aging by PCR differential display method. J. Mol. Neurosci. 8:1997;13-18.
144. Wu Y., Sun F., Tong D.M. Changes in membrane properties during energy depletion-induced cell injury studied with fluorescence microscopy. Biophys. J. 71:1996;91-100.
145. Wurtman R.J. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci. 15:1992;117-122.
146. Xie L., Helmerhorst E., Taddel K., Plewright B., van Bronswijk W., Martins R. Alzheimer's β-amyloid peptides compete for insulin binding to the insulin receptor. J. Neurosci. 22(RC221):2002;1-5.
147. Xu H., Sweeney D., Wang R., Thinakaran G., Lo A.C., Sisodia S.S., Greengard P., Gandy S. Generation of Alzheimer beta-amyloid protein in the trans-Golgi network in the apparent abscence of vesicle formation. Proc. Natl. Acad. Sci. U. S. A. 94:1997;3748-3752.
148. Zahniser N.R., Goens M.B., Hanaway P.J., Vinych J.V. Characterization and regulation of insulin receptors in rat brain. J. Neurochem. 42:1984;1354-1362.