Systemic and brain metabolic dysfunction as a new paradigm for approaching Alzheimer's dementia

Neurochemical Research

Volumn 32, Issue 4-5, 2007, Pages 555-567

  Giordano, Vincenzo ^a   Peluso, Gianfranco ^b   Iannuccelli, Maurizio ^a   Benatti, Paola ^a   Nicolai, Raffaella ^a   Calvani, Menotti ^a  

^a Scientific Department   (Italy)

^b Institute of Protein Biochemistry   (Italy)

Author keywords

Adiponectin; Alzheimer's disease; Cholesterol; Ghrelin; Insulin; Leptin

Indexed keywords

ADIPONECTIN; ALPHA KETO GLUTARATE DEHYDROGENASE; ALPHA SYNUCLEIN; ALPHA TOCOPHEROL; ALUMINUM; AMYLIN; AMYLOID BETA PROTEIN; APOLIPOPROTEIN E4; ASCORBIC ACID; CHOLESTEROL; CHOLINESTERASE INHIBITOR; CYANOCOBALAMIN; ENZYME; FOLIC ACID; GHRELIN; GLUCOSE; GROWTH HORMONE RECEPTOR; HOMOCYSTEINE; INSULIN; INSULINASE; LEPTIN; MEMBRANE METALLOENDOPEPTIDASE; PLASMIN; S ADENOSYLMETHIONINE; SOMATOMEDIN C; TAU PROTEIN; UNCLASSIFIED DRUG;

ALZHEIMER DISEASE; ATHEROSCLEROSIS; BLOOD BRAIN BARRIER; BRAIN DYSFUNCTION; BRAIN METABOLISM; CHOLINERGIC NERVE CELL; DNA SYNTHESIS; DOWN SYNDROME; GENE EXPRESSION; GLUCOSE METABOLISM; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; INSULIN SENSITIVITY; KNOCKOUT MOUSE; LIPID METABOLISM; LIPID RAFT; LIPOGENESIS; LONG TERM POTENTIATION; METABOLIC SYNDROME X; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; PRIORITY JOURNAL; REVIEW; RISK FACTOR; STROKE; SYMPTOM; TELENCEPHALON; TRANSGENIC ANIMAL;

ADIPONECTIN; ALZHEIMER DISEASE; APOLIPOPROTEINS E; BRAIN CHEMISTRY; CHOLESTEROL; FEMALE; HISTORY, 20TH CENTURY; HUMANS; INSULIN; INSULIN-LIKE GROWTH FACTOR I; LEPTIN; METABOLIC DISEASES; MIDDLE AGED; PEPTIDE HORMONES;

EID: 33947581042     PISSN: 03643190     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11064-006-9125-8     Document Type: Review

References (176)

1. Alzheimer A, Alzheimer A (1907) Über eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift für Psychiatrie und psychisch- gerichtliche Medizin, Berlin 64:146-148
2. Pearce JM (2000) Alzheimer's disease. J Neurol Neurosurg Psychiatry 68(3):348
3. Abdul HM, Calabrese V, Calvani M, Butterfield DA (2006) Acetyl-L-carnitine-induced up-regulation of heat shock proteins protects cortical neurons against amyloid-beta peptide 1-42-mediated oxidative stress and neurotoxicity: implications for Alzheimer's disease. J Neurosci Res 84(2):398-408
4. Levy ML, Cummings JL, Fairbanks LA, Bravi D, Calvani M, Carta A (1996) Longitudinal assessment of symptoms of depression, agitation, and psychosis in 181 patients with Alzheimer's disease. Am J Psychiatry 153(11):1438-1443
5. Schwartz P (1975) Amyloidosis, expression and cause of presenile and senile mental and physical regression. A revision of the amyloid problem. Zentralbl Allg Pathol 119(6):533-548
6. Wisniewski HM, Narang HK, Terry RD (1976) Neurofibrillary tangles of paired helical filaments. J Neurol Sci 27(2):173-181
7. Roth M, Tomlinson BE, Blessed G (1966) Correlation between scores for dementia and counts of 'senile plaques' in cerebral grey matter of elderly subjects. Nature 209(18):109-110
8. Roth M, Tomlinson BE, Blessed G (1967) The relationship between quantitative measures of dementia and of degenerative changes in the cerebral grey matter of elderly subjects. Proc R Soc Med 60(3):254-260
9. Blessed G, Tomlinson BE, Roth M (1968) The association between quantitative measures of dementia and of senile change in the cerebral grey matter of elderly subjects. Br J Psychiatry 114(512):797-811
10. Rabins PV, Folstein MF (1983) The dementia patient: evaluation and care. Geriatrics 38(8):99-103
11. Tune L, Gucker S, Folstein M, Oshida L, Coyle JT (1985) Cerebrospinal fluid acetylcholinesterase activity in senile dementia of the Alzheimer type. Ann Neurol 17(1):46-48
12. Pearlson GD, Tune LE (1986) Cerebral ventricular size and cerebrospinal fluid acetylcholinesterase levels in senile dementia of the Alzheimer type. Psychiatry Res 17(1):23-29
13. Burch EA Jr, Andrews SR (1987) Comparison of two cognitive rating scales in medically ill patients. Int J Psychiatry Med 17(2):193-200
14. Klatzo I, Wisniewski H, Streicher E (1965) Experimental production of neurofibrillary degeneration 1, light microscopic observations. J Neuropathol Exp Neurol 24:187-199
15. Terry RD, Pena C (1965) Experimental production of neurofibrillary degeneration 2, electron microscopy, phosphatase histochemistry and electron probe analysis. J Neuropathol Exp Neurol 24:200-210
16. Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Trans Am Neurol Assoc 98:17-20
17. Crapper DR, Krishnan SS, Dalton AJ (1973) Brain aluminum distribution in Alzheimer's disease and experimental neurofibrillary degeneration. Science 180(85):511-513
18. Crapper DR, Krishnan SS, Quittkat S (1976) Aluminium, neurofibrillary degeneration and Alzheimer's disease. Brain 99(1):67-80
19. Vatassery GT, Maletta GJ (1983) Relationship between nutrition and dementia in the elderly. Psychiatr Med 1(4):429-443
20. Davies P, Maloney AJ (1976) Selective loss of central cholinergic neurons in Alzheimer's disease. Lancet 2(8000):1403
21. Perry E, Walker M, Grace J, Perry R (1999) Acetylcholine in mind: a neurotransmitter correlate of consciousness?. Trends Neurosci 22:273-280
22. Whitehouse PJ, Price DL, Clark AW, Coyle JT, DeLong MR (1981) Alzheimer disease: evidence for selective loss of cholinergic neurons in the nucleus basalis. Ann Neurol 10(2):122-126
23. Bales KR, Tzavara ET, Wu S, Wade MR, Bymaster FP, Paul SM, Nomikos GG (2006) Cholinergic dysfunction in a mouse model of Alzheimer disease is reversed by an anti-A beta antibody. J Clin Invest 116(3):825-832
24. Calvani M, Carta A (1991) Clinical issues of cognitive enhancers in Alzheimer disease. Alzheimer Dis Assoc Disord 5(S1):25-31
25. Chapel HM, Esiri MM, Wilcock GK (1984) Immunoglobulin and other proteins in the cerebrospinal fluid of patients with Alzheimer's disease. J Clin Pathol 37(6):697-699
26. Wolozin BL, Pruchnicki A, Dickson DW, Davies P (1986) A neuronal antigen in the brains of Alzheimer patients. Science 232(4750):648-650
27. Jakes R, Spillantini MG, Goedert M (1994) Identification of two distinct synucleins from human brain. FEBS Lett 345(1):27-32
28. Mudher A, Lovestone S (2002) Alzheimer's disease-do tauists and baptists finally shake hands? Trends Neurosci 25(1):22-26
29. Trojanowski JQ (2002) Tauists, Baptists, Syners, Apostates, and new data. Ann Neurol 52(3):263-265
30. Masliah E, Terry RD, Mallory M, Alford M, Hansen LA (1990) Diffuse plaques do not accentuate synapse loss in Alzheimer's disease. Am J Pathol 137(6):1293-1297
31. Honer WG (2003) Pathology of presynaptic proteins in Alzheimer's disease: more than simple loss of terminals. Neurobiol Aging 24(8):1047-1062
32. Butterfield DA (1997) Beta-Amyloid-associated free radical oxidative stress and neurotoxicity: implications for Alzheimer's disease. Chem Res Toxicol 10(5):495-506
33. Butterfield DA, Hensley K, Cole P, Subramaniam R, Aksenov M, Aksenova M, Bummer PM, Haley BE, Carney JM (1997) Oxidatively induced structural alteration of glutamine synthetase assessed by analysis of spin label incorporation kinetics: relevance to Alzheimer's disease. J Neurochem 68(6):2451-2457
34. Subramaniam R, Roediger F, Jordan B, Mattson MP, Keller JN, Waeg G, Butterfield DA (1997) The lipid peroxidation product, 4-hydroxy-2-trans-nonenal, alters the conformation of cortical synaptosomal membrane proteins. J Neurochem 69(3):1161-1169
35. Koppal T, Drake J, Yatin S, Jordan B, Varadarajan S, Bettenhausen L, Butterfield DA (1999) Peroxynitrite-induced alterations in synaptosomal membrane proteins: insight into oxidative stress in Alzheimer's disease. J Neurochem 72(1):310-317
36. Halliwell B, Gutteridge JMC (1985) Oxygen radicals and the nervous system. Trends in Neurosciences 8:22-26
37. Muller DP, Metcalfe T, Bowen DM (1986) Vitamin E in brains of patients with Alzheimer's disease and Down's syndrome. Lancet 1(8489):1093-1094
38. Metcalfe T, Bowen DM, Muller DP (1989) Vitamin E concentrations in human brain of patients with Alzheimer's disease, fetuses with Down's syndrome, centenarians, and controls. Neurochem Res 14(12):1209-1212
39. Zaman Z, Roche S, Fielden P, Frost PG, Niriella DC, Cayley AC (1992) Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease. Age Ageing 21(2):91-94
40. Tohgi H, Abe T, Nakanishi M, Hamato F, Sasaki K, Takahashi S (1994) Concentrations of alpha-tocopherol and its quinone derivative in cerebrospinal fluid from patients with vascular dementia of the Binswanger type and Alzheimer type dementia. Neurosci Lett 174(1):73-76
41. Jimenez-Jimenez FJ, de Bustos F, Molina JA, Benito-Leon J, Tallon-Barranco A, Gasalla T, Orti-Pareja M, Guillamon F, Rubio JC, Arenas J, Enriquez-de-Salamanca R (1997) Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer's disease. J Neural Transm 104(6-7):703-710
42. Sano M, Ernesto C, Thomas RG et al (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. N Engl J Med 336:1216-1222
43. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, Galasko D, Jin S, Kaye J, Levey A, Pfeiffer E, Sano M, van Dyck CH, Thal LJ (2005) Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med 352(23):2379-2388
44. Fillenbaum GG, Kuchibhatla MN, Hanlon JT, Artz MB, Pieper CF, Schmader KE, Dysken MW, Gray SL (2005) Dementia and Alzheimer's disease in community-dwelling elders taking vitamin C and/or vitamin E. Ann Pharmacother 39(12):2009-2014
45. McCaddon A, Kelly CL (1992) Alzheimers disease: a 'cobalaminergic' hypothesis. Med Hypotheses 37:161-165
46. Cole MG, Prchal JF (1984) Low serum vitamin B12 in Alzheimer-type dementia. Age Ageing 13(2):101-105
47. Ikeda T, Furukawa Y, Mashimoto S, Takahashi K, Yamada M (1990) Vitamin B12 levels in serum and cerebrospinal fluid of people with Alzheimer's disease. Acta Psychiatr Scand 82(4):327-329
48. Malouf M, Grimley EJ, Areosa SA (2003) Folic acid with or without vitamin B12 for cognition and dementia. Cochrane Database Syst Rev 4:CD004514
49. Kruman II, Kumaravel TS, Lohani A, Pedersen WA, Cutler RG, Kruman Y, Haughey N, Lee J, Evans M, Mattson MP (2002) Folic acid deficiency and homocysteine impair DNA repair in hippocampal neurons and sensitize them to amyloid toxicity in experimental models of Alzheimer's disease. J Neurosci 22(5):1752-1762
50. Regland B, Gottfries CG (1992) Slowed synthesis of DNA and methionine is a pathogenetic mechanism common to dementia in Down's syndrome, AIDS and Alzheimer's disease?. Med Hypotheses 38(1):11-19
51. Blass JP, Sheu RK, Gibson GE (2000) Inherent abnormalities in energy metabolism in Alzheimer disease. Interaction with cerebrovascular compromise. Ann N Y Acad Sci 903:204-221
52. Bubber P, Haroutunian V, Fisch G, Blass JP, Gibson GE (2005) Mitochondrial abnormalities in Alzheimer brain: mechanistic implications. Ann Neurol 57(5):695-703
53. Cash AD, Perry G, Ogawa O, Raina AK, Zhu X, Smith MA (2002) Is Alzheimer's disease a mitochondrial disorder? Neuroscientist 8(5):489-496
54. Gibson GE, Sheu KF, Blass JP (1998) Abnormalities of mitochondrial enzymes in Alzheimer disease. J Neural Transm 105(8-9):855-870
55. Gibson GE, Park LC, Sheu KF, Blass JP, Calingasan NY (2000) The alpha-ketoglutarate dehydrogenase complex in neurodegeneration. Neurochem Int 36(2):97-112
56. Makar TK, Cooper AJ, Tofel-Grehl B, Thaler HT, Blass JP (1995) Carnitine, carnitine acetyltransferase, and glutathione in Alzheimer brain. Neurochem Res 20(6):705-711
57. Rai G, Wright G, Scott L, Beston B, Rest J, Exton-Smith AN (1990) Double-blind, placebo controlled study of acetyl-1-carnitine in patients with Alzheimer's dementia. Curr Med Res Opin 11(10):638-647
58. Passeri M, Cucinotta D, Bonati PA, Iannuccelli M, Parnetti L, Senin U (1990) Acetyl-L-carnitine in the treatment of mildly demented elderly patients. Int J Clin Pharmacol Res 10(1-2):75-79
59. Carta A, Calvani M (1991) Acetyl-L-carnitine: a drug able to slow the progress of Alzheimer's disease? Ann N Y Acad Sci 640:228-232
60. Spagnoli A, Lucca U, Menasce G, Bandiera L, Cizza G, Forloni G, Tettamanti M, Frattura L, Tiraboschi P, Pomelli M et al (1991) Long-term acetyl-L-carnitine treatment in Alzheimer's disease. Neurology 41(11):1726-1732
61. Sano M, Bell K, Cote L, Dooneief G, Lawton A, Legler L, Marder K, Naini A, Stern Y, Mayeux R (1992) Double-blind parallel design pilot study of acetyl levocarnitine in patients with Alzheimer's disease. Arch Neurol 49(11):1137-1141
62. Carta A, Calvani M, Bravi D, Bhuachalla SN (1993) Acetyl-L- carnitine and Alzheimer's disease: pharmacological considerations beyond the cholinergic sphere. Ann N Y Acad Sci 695:324-326
63. Thal LJ, Calvani M, Amato A, Carta A (2000) A 1-year controlled trial of acetyl-l-carnitine in early-onset AD. Neurology 55(6):805-810
64. Montgomery SA, Thal LJ, Amrein R (2003) Meta-analysis of double blind randomized controlled clinical trials of acetyl-L-carnitine versus placebo in the treatment of mild cognitive impairment and mild Alzheimer's disease. Int Clin Psychopharmacol 18(2):61-71
65. Gibson GE, Haroutunian V, Zhang H, Park LC, Shi Q, Lesser M, Mohs RC, Sheu RK, Blass JP (2000) Mitochondrial damage in Alzheimer's disease varies with apolipoprotein E genotype. Ann Neurol 48(3):297-303
66. Strittmatter WJ, Saunders AM, Schmechel D, Pericak-Vance M, Enghild J, Salvesen GS, Roses AD (1993) Apolipoprotein E: high-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc Natl Acad Sci USA 90(5):1977-1981
67. Strittmatter WJ, Weisgraber KH, Huang DY, Dong LM, Salvesen GS, Pericak-Vance M, Schmechel D, Saunders AM, Goldgaber D, Roses AD (1993) Binding of human apolipoprotein E to synthetic amyloid beta peptide: isoform-specific effects and implications for late-onset Alzheimer disease. Proc Natl Acad Sci USA 90(17):8098-8102
68. Roses AD (1996) Apolipoprotein E in neurology. Curr Opin Neurol 9(4):265-270
69. Muckle TJ, Roy JR (1985) High-density lipoprotein cholesterol in differential diagnosis of senile dementia. Lancet 1(8439):1191-1193
70. Nelson TJ, Alkon DL (2005) Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration. Biochem Soc Trans 33(5):1033-1036
71. Lane RM, Farlow MR (2005) Lipid homeostasis and apolipoprotein E in the development and progression of Alzheimer's disease. J Lipid Res 46(5):949-968
72. Kabara JJ (1973) A critical review of brain cholesterol metabolism. Prog Brain Res 40:363-382
73. Bjorkhem I (2002) Do oxysterols control cholesterol homeostasis? J Clin Invest 110(6):725-730
74. Bjorkhem I, Meaney S (2004) Brain cholesterol: long secret life behind a barrier. Arterioscler Thromb Vasc Biol 24(5):806-815
75. Ercoli A, Di Frisco S, De Ruggeri P (1953) Isolation, constitution and biological significance of cerebrosterol, a companion of cholesterol in the horse brain. Boll Soc Ital Biol Sper 29(4):494-497
76. Di Frisco S, De Ruggieri P, Ercoli A (1953) Isolation of cerebrosterol from human brain. Boll Soc Ital Biol Sper 29(7):1351-1352
77. Dhar AK, Teng JI, Smith LL (1973) Biosynthesis of cholest-5-ene-3beta, 24-diol (cerebrosterol) by bovine cerebral cortical microsomes. J Neurochem 21(1):51-60
78. Lutjohann D, Breuer O, Ahlborg G, Nennesmo I, Siden A, Diczfalusy U, Bjorkhem I (1996) Cholesterol homeostasis in human brain: evidence for an age-dependent flux of 24S-hydroxycholesterol from the brain into the circulation. Proc Natl Acad Sci USA 93(18):9799-9804
79. Papassotiropoulos A, Lutjohann D, Bagli M, Locatelli S, Jessen F, Rao ML, Maier W, Bjorkhem I, von Bergmann K, Heun R (2000) Plasma 24S- hydroxycholesterol: a peripheral indicator of neuronal degeneration and potential state marker for Alzheimer's disease. Neuroreport 11(9):1959-1962
80. Lutjohann D, Papassotiropoulos A, Bjorkhem I, Locatelli S, Bagli M, Oehring RD, Schlegel U, Jessen F, Rao ML, von Bergmann K, Heun R (2000) Plasma 24S-hydroxycholesterol (cerebrosterol) is increased in Alzheimer and vascular demented patients. J Lipid Res 41(2):195-198
81. Alexandrov P, Cui JG, Zhao Y, Lukiw WJ (2005) 24S-hydroxycholesterol induces inflammatory gene expression in primary human neural cells. Neuroreport 16(9):909-913
82. Kolsch H, Ludwig M, Lutjohann D, Rao ML (2001) Neurotoxicity of 24-hydroxycholesterol, an important cholesterol elimination product of the brain, may be prevented by vitamin E and estradiol-17beta. J Neural Transm 108(4):475-488
83. Heverin M, Bogdanovic N, Lutjohann D, Bayer T, Pikuleva I, Bretillon L, Diczfalusy U, Winblad B, Bjorkhem I (2004) Changes in the levels of cerebral and extracerebral sterols in the brain of patients with Alzheimer's disease. J Lipid Res 45(1):186-193
84. Boyles JK, Pitas RE, Wilson E, Mahley RW, Taylor JM (1985) Apolipoprotein E associated with astrocytic glia of the central nervous system and with nonmyelinating glia of the peripheral nervous system. J Clin Invest 76(4):1501-1513
85. Pitas RE, Boyles JK, Lee SH, Hui D, Weisgraber KH (1987) Lipoproteins and their receptors in the central nervous system. Characterization of the lipoproteins in cerebrospinal fluid and identification of apolipoprotein B,E(LDL) receptors in the brain. J Biol Chem 262(29):14352-14360
86. Boyles JK, Zoellner CD, Anderson LJ, Kosik LM, Pitas RE, Weisgraber KH, Hui DY, Mahley RW, Gebicke-Haerter PJ, Ignatius MJ et al (1989) A role for apolipoprotein E, apolipoprotein A-I, and low density lipoprotein receptors in cholesterol transport during regeneration and remyelination of the rat sciatic nerve. J Clin Invest 83(3):1015-1031
87. Petegnief V, Saura J, de Gregorio-Rocasolano N, Paul SM (2001) Neuronal injury-induced expression and release of apolipoprotein E in mixed neuron/glia co-cultures: nuclear factor kappaB inhibitors reduce basal and lesion-induced secretion of apolipoprotein E. Neuroscience 104(1):223-2334
88. Cordy JM, Hooper NM, Turner AJ (2006) The involvement of lipid rafts in Alzheimer's disease. Mol Membr Biol 23(1):111-122
89. Pappolla MA, Bryant-Thomas TK, Herbert D, Pacheco J, Fabra Garcia M, Manjon M, Girones X, Henry TL, Matsubara E, Zambon D, Wolozin B, Sano M, Cruz-Sanchez FF, Thal LJ, Petanceska SS, Refolo LM (2003) Mild hypercholesterolemia is an early risk factor for the development of Alzheimer amyloid pathology. Neurology 61(2):199-205
90. Osborne AR, Pollock VV, Lagor WR, Ness GC (2004) Identification of insulin-responsive regions in the HMGCoA reductase promoter. Biochem Biophys Res Commun 318(4):814-818
91. Simonen P, Gylling H, Howard AN, Miettinen TA (2000) Introducing a new component of the metabolic syndrome: low cholesterol absorption. Am J Clin Nutr 72(1):82-88
92. Simonen PP, Gylling HK, Miettinen TA (2002) Diabetes contributes to cholesterol metabolism regardless of obesity. Diabetes Care 25(9):1511-1515
93. Twisk J, Hoekman MF, Lehmann EM, Meijer P, Mager WH, Princen HM (1995) Insulin suppresses bile acid synthesis in cultured rat hepatocytes by down-regulation of cholesterol 7 alpha-hydroxylase and sterol 27-hydroxylase gene transcription. Hepatology 21(2):501-510
94. Carro E, Torres-Aleman I (2004) Insulin-like growth factor I and Alzheimer's disease: therapeutic prospects? Expert Rev Neurother 4(1):79-86
95. de la Monte SM, Wands JR (2005) 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 7(1):45-61
96. Frolich L, Blum-Degen D, Riederer P, Hoyer S (1999) A disturbance in the neuronal insulin receptor signal transduction in sporadic Alzheimer's disease. Ann N Y Acad Sci 893:290-293
97. Hoyer S (1998) Is sporadic Alzheimer disease the brain type of non-insulin dependent diabetes mellitus? A challenging hypothesis. J Neural Transm 105(4-5):415-422
98. Yan Z, Feng J (2004) Alzheimer's disease: interactions between cholinergic functions and beta-amyloid. Curr Alzheimer Res 1(4):241-248
99. Biessels GJ, Kappelle LJ (2005) Increased risk of Alzheimer's disease in Type II diabetes: insulin resistance of the brain or insulin-induced amyloid pathology? Biochem Soc Trans 33(Pt 5):1041-1044
100. Zhang J, Slevin M, Duraisamy Y, Gaffney JA, Smith C, Ahmed N (2006) Comparison of protective effects of aspirin, d-penicillamine and vitamin E against high glucose-mediated toxicity in cultured endothelial cells. Biochim Biophys Acta 1762(5):551-557
101. Li SY, Fang CX, Aberle NS 2nd, Ren BH, Ceylan-Isik AF, Ren J. 2005 Inhibition of PI-3 kinase/Akt/mTOR, but not calcineurin signaling, reverses insulin-like growth factor I-induced protection against glucose toxicity in cardiomyocyte contractile function. J Endocrinol 186(3):491-503
102. der Voort PH, Feenstra RA, Bakker AJ, Heide L, Boerma EC, der Horst IC (2006) Intravenous glucose intake independently related to intensive care unit and hospital mortality: an argument for glucose toxicity in critically ill patients. Clin Endocrinol 64(2):141-145
103. Gispen WH, Biessels GJ (2000) Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23(11):542-549
104. Gasparini L, Xu H (2003) Potential roles of insulin and IGF-1 in Alzheimer's disease. Trends Neurosci 26(8):404-406
105. Blass JP, Zemcov A (1984) Alzheimer's disease. A metabolic systems degeneration? Neurochem Pathol 2(2):103-114
106. Blass JP, Gibson GE (1992) Nonneural markers in Alzheimer disease. Alzheimer Dis Assoc Disord 6(4):205-224
107. Blass JP, Gibson GE, Sheu KF (1997) Peripheral markers of Alzheimer's disease. Aging 9(4S):55-56
108. Gasparini L, Racchi M, Binetti G, Trabucchi M, Solerte SB, Alkon D, Etcheberrigaray R, Gibson G, Blass J, Paoletti R, Govoni S (1998) Peripheral markers in testing pathophysiological hypotheses and diagnosing Alzheimer's disease. FASEB J 12(1):17-34
109. Sorbi S, Bird ED, Blass JP (1983) Decreased pyruvate dehydrogenase complex activity in Huntington and Alzheimer brain. Ann Neurol 13(1):72-78
110. Sheu KF, Kim YT, Blass JP, Weksler ME (1985) An immunochemical study of the pyruvate dehydrogenase deficit in Alzheimer's disease brain. Ann Neurol 17(5):444-449
111. Peterson C, Gibson GE, Blass JP (1985) Altered calcium uptake in cultured skin fibroblasts from patients with Alzheimer's disease. N Engl J Med 312(16):1063-1065
112. Sims NR, Finegan JM, Blass JP (1987) Altered metabolic properties of cultured skin fibroblasts in Alzheimer's disease. Ann Neurol 21(5):451-457
113. Sims NR, Finegan JM, Blass JP (1985) Altered glucose metabolism in fibroblasts from patients with Alzheimer's disease. N Engl J Med 313(10):638-639
114. Balin AK, Baker AC, Leong IC, Blass JP (1988) Normal replicative lifespan of Alzheimer skin fibroblasts. Neurobiol Aging 9(2):195-198
115. Sims NR, Blass JP (1986) Phosphofructokinase activity in fibroblasts from patients with Alzheimer's disease and ageand sex-matched controls. Metab Brain Dis 1(1):83-90
116. Sims NR, Blass JP, Murphy C, Bowen DM, Neary D (1987) Phosphofructokinase activity in the brain in Alzheimer's disease. Ann Neurol 21(5):509-510
117. Blass JP, Baker AC, Ko L, Sheu RK, Black RS (1991) Expression of 'Alzheimer antigens' in cultured skin fibroblasts. Arch Neurol 48(7):709-717
118. Sheu KF, Cooper AJ, Koike K, Koike M, Lindsay JG, Blass JP (1994) Abnormality of the alpha-ketoglutarate dehydrogenase complex in fibroblasts from familial Alzheimer's disease. Ann Neurol 35(3):312-318
119. Gibson G, Martins R, Blass J, Gandy S (1996) Altered oxidation and signal transduction systems in fibroblasts from Alzheimer patients. Life Sci 59(5-6):477-489
120. Blass JP, Hanin I, Barclay L, Kopp U, Reding MJ (1985) Red blood cell abnormalities in Alzheimer disease. J Am Geriatr Soc 33(6):401-405
121. Sherman KA, Gibson GE, Blass JP (1986) Human red blood cell choline uptake with age and Alzheimer's disease. Neurobiol Aging 7(3):205-209
122. Gibson GE, Nielsen P, Sherman KA, Blass JP (1987) Diminished mitogen-induced calcium uptake by lymphocytes from Alzheimer patients. Biol Psychiatry 22(9):1079-1086
123. Sims NR, Finegan JM, Blass JP, Bowen DM, Neary D (1987) Mitochondrial function in brain tissue in primary degenerative dementia. Brain Res 436(1):30-38
124. Gibson GE, Sheu KF, Blass JP, Baker A, Carlson KC, Harding B, Perrino P (1988) Reduced activities of thiamine-dependent enzymes in the brains and peripheral tissues of patients with Alzheimer's disease. Arch Neurol 45(8):836-840
125. Sheu KF, Clarke DD, Kim YT, Blass JP, Harding BJ, DeCicco J (1988) Studies of transketolase abnormality in Alzheimer's disease. Arch Neurol 45(8):841-845
126. Blass JP (1993) Metabolic alterations common to neural and non-neural cells in Alzheimer's disease. Hippocampus 3S:45-53
127. Giaquinto S, Nolfe G, Calvani M. 1985 Cluster analysis of cognitive performance in elderly and demented subjects. Ital J Neurol Sci 6(2):157-165
128. Borenstein AR, Copenhaver CI, Mortimer JA (2006) Earlylife risk factors for Alzheimer disease. Alzheimer Dis Assoc Disord 20(1):63-72
129. Whalley LJ, Dick FD, McNeill G. 2006 A life-course approach to the aetiology of late-onset dementias. Lancet Neurol 5(1):87-96
130. Hales CN, Barker DJ (1992) Type 2 (non-insulin-dependent) diabetes mellitus: the thrifty phenotype hypothesis. Diabetologia 35(7):595-601
131. Luchsinger JA, Mayeux R (2004) Cardiovascular risk factors and Alzheimer's disease. Curr Atheroscler Rep 6(4):261-266
132. Messier C, Teutenberg K (2005) The role of insulin, insulin growth factor, and insulin-degrading enzyme in brain aging and Alzheimer's disease. Neural Plast 12(4):311-328
133. Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hanninen T, Pyorala K, Riekkinen P, Laakso M (1993) Essential hypertension and cognitive function. The role of hyperinsulinemia. Hypertension 22(5):771-779
134. Kuusisto J, Koivisto K, Mykkanen L, Helkala EL, Vanhanen M, Hanninen T, Kervinen K, Kesaniemi YA, Riekkinen PJ, Laakso M (1997) Association between features of the insulin resistance syndrome and Alzheimer's disease independently of apolipoprotein E4 phenotype: cross sectional population based study. BMJ 315(7115):1045-1049
135. Kernan WN, Inzucchi. SE, Viscoli CM, Brass LM, Bravata DM, Horwitz RI (2002) Insulin resistance and risk for stroke. Neurology 24;59(6):809-815
136. Golden SH, Folsom AR, Coresh J, Sharrett AR, Szklo M, Brancati F (2002) Risk factor groupings related to insulin resistance and their synergistic effects on subclinical atherosclerosis: the atherosclerosis risk in communities study. Diabetes 51(10):3069-3076
137. Yaffe K, Kanaya A, Lindquist K, Simonsick EM, Harris T, Shorr RI, Tylavsky FA, Newman AB (2004) The metabolic syndrome, inflammation, and risk of cognitive decline. JAMA 292(18):2237-2242
138. Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404:661-671
139. Calvani M, Benatti P, Mancinelli A, D'Iddio S, Giordano V, Koverech A, Amato A, Brass EP (2004) Carnitine replacement in end-stage renal disease and hemodialysis. Ann N Y Acad Sci 1033:52-66
140. Ahima RS (2005) Central actions of adipocyte hormones. Trends Endocrinol Metab 16(7):307-313
141. Couce ME, Burguera B, Parisi JE, Jensen MD, Lloyd RV (1997) Localization of leptin receptor in the human brain. Neuroendocrinology 66:145-150
142. Shanley LJ, Irving AJ, Rae MG, Ashford ML, Harvey J (2002) Leptin inhibits rat hippocampal neurons via activation of large conductance calcium-activated K+ channels. Nat Neurosci 5:299-300
143. Harvey J, Shanley LJ, O'Malley D, Irving AJ (2005) Leptin: a potential cognitive enhancer?. Biochem Soc Trans. 33(Pt 5):1029-1032
144. Li XL, Aou S, Oomura Y, Hori N, Fukunaga K, Hori T (2002) Impairment of long-term potentiation and spatial memory in leptin receptor-deficient rodents. Neuroscience 113(3):607-615
145. Valerio A, Ghisi V, Dossena M, Tonello C, Giordano A, Frontini A, Ferrario M, Pizzi M, Spano P, Carruba MO, Nisoli E (2006) Leptin increases axonal growth cone size in developing mouse cortical neurons by convergent signals inactivating glycogen synthase kinase-3beta. J Biol Chem. 281(18):12950-12958
146. Fewlass DC, Noboa K, Pi-Sunyer FX, Johnston JM, Yan SD, Tezapsidis N (2004) Obesity-related leptin regulates Alzheimer's Abeta. FASEB J 18(15):1870-1878
147. Counts SE, Perez SE, Ginsberg SD, De Lacalle S, Mufson EJ (2003) Galanin in Alzheimer disease. Mol Interv 3(3):137-156
148. Cheung CC, Hohmann JG, Clifton DK, Steiner RA (2001) Distribution of galanin messenger RNA-expressing cells in murine brain and their regulation by leptin in regions of the hypothalamus. Neuroscience 103:423-432
149. Olsson T, Nasman B, Rasmuson S, Ahren B (1998) Dual relation between leptin and cortisol in humans is disturbed in Alzheimer's disease. Biol Psychiatry 44(5):374-376
150. Power DA, Noel J, Collins R, O'Neill D (2001) Circulating leptin levels and weight loss in Alzheimer's disease patients. Dement Geriatr Cogn Disord 12(2):167-170
151. Intebi AD, Garau L, Brusco I, Pagano M, Gaillard RC, Spinedi E. 2002-(2003) Alzheimer's disease patients display gender dimorphism in circulating anorectic adipokines. Neuroimmunomodulation 10(6):351-358
152. Koivisto AM, Helisalmi S, Pihlajamaki J, Moilanen L, Kuusisto J, Laakso M, Hiltunen M, Keijo K, Hanninen T, Helkala EL, Kervinen K, Kesaniemi YA, Soininen H (2005) Interleukin-6 promoter polymorphism and late-onset Alzheimer's disease in the Finnish population. J Neurogenet 19(3):155-161
153. Ikeda M, Brown J, Holland AJ, Fukuhara R, Hodges JR (2002) Changes in appetite, food preference, and eating habits in frontotemporal dementia and Alzheimer's disease. J Neurol Neurosurg Psychiatry Oct;73(4):371-376
154. Wang PN, Yang CL, Lin KN, Chen WT, Chwang LC, Liu HC (2004) Weight loss, nutritional status and physical activity in patients with Alzheimer's disease. A controlled study. J Neurol 251(3):314-320
155. Kojima M, Hosoda H, Date Y, Nakazato M, Kangawa K (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656-660
156. Tschop M, Smiley DL, Heiman ML (2000) Ghrelin induces adiposity in rodents. Nature 407:908-913
157. van der Lely AJ, Tschop M, Heiman ML, Ghigo E (2004) Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 25:426-457
158. Horvath TL, Castañeda T, Tang-Christensen M, Pagotto U, Tschop MH (2003) Ghrelin as a potential anti-obesity target. Curr Pharm Des 9:1383-1395
159. Kojima M, Kangawa K (2005) Ghrelin: structure and function. Physiol Rev 85:495-522
160. Valera Mora ME, Scarfone A, Valenza V, Calvani M, Greco AV, Gasbarrini G, Mingrone G (2005) Ghrelin does not influence gastric emptying in obese subjects. Obes Res 13(4):739-744
161. Hou Z, Miao Y, Gao L, Pan H, Zhu S (2006) Ghrelin-containing neuron in cerebral cortex and hypothalamus linked with the DVC of brainstem in rat. Regul Pept 134(2-3):126-131
162. Yamada KA, Sleeman MW, Tschop MH, Horvath TL (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9(3):381-388
163. Diano S, Farr SA, Benoit SC, McNay EC, da Silva I, Horvath B, Gaskin FS, Nonaka N, Jaeger LB, Banks WA, Morley JE, Pinto S, Sherwin RS, Xu L, Yamada KA, Sleeman MW, Tschop MH, Horvath TL (2006) Ghrelin controls hippocampal spine synapse density and memory performance. Nat Neurosci 9(3):381-388
164. Berg AH, Combs TP, Scherer PE (2002) ACRP30-adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol Metab 13:84-89
165. Calvani M, Scarfone A, Granato L, Mora EV, Nanni G, Castagneto M, Greco AV, Manco M, Mingrone G (2004) Restoration of adiponectin pulsatility in severely obese subjects after weight loss. Diabetes 53(4):939-947
166. Kadowaki T, Yamauchi T (2005) Adiponectin and adiponectin receptors. Endocr Rev 26:439-451
167. Tsao TS, Lodish HF, Fruebis J (2002) ACRP30, a new hormone controlling fat and glucose metabolism. Eur JPharmacol 440:213-221
168. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, Noda, Tl (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277:25863-25866
169. Maeda NShimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin-ACRP30. Nature Med 8:731-737
170. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tob K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nature Med 7:941-946
171. Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J BiolChem 271:10697-10703
172. Weyer C et al (2001) Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab 86:1930-1935
173. Statnick MA et al (2000) Decreased expression of apM1 in omental and subcutaneous adipose tissue of humans with type 2 diabetes. Int J Exp Diabetes Res 1:81-88
174. Hotta K, Funahashi T, Arita Y, Takahashi M, Matsuda M, Okamoto Y, Iwahashi H, Kuriyama H, Ouchi N, Maeda K, Nishida M, Kihara S, Sakai N, Nakajima T, Hasegawa K, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Hanafusa T, Matsuzawa Y (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20:1595-1599
175. Spranger J, Verma S, Gohring I, Bobbert T, Seifert J, Sindler AL, Pfeiffer A, Hileman SM, Tschop M, Banks WA (2006) Adiponectin does not cross the blood-brain barrier but modifies cytokine expression of brain endothelial cells. Diabetes 55(1):141-147
176. Zuliani G, Ronzini M, Guerra G, Rossi L, Munari MR, Zurlo A, Volpato S, Atti AR, Ble A, Fellin RJ (2006) Plasma cytokines profile in older subjects with late onset Alzheimer's disease or vascular dementia. Psychiat Res (in press)