Is Amyloid-β an Innocent Bystander and Marker in Alzheimer's Disease? Is the Liability of Multivalent Cation Homeostasis and its Influence on Amyloid-β Function the Real Mechanism?

Journal of Alzheimer's Disease

Volumn 42, Issue 1, 2014, Pages 69-85

  Manafirad, Arash ^a   Farzadfar, Farshad ^b   Habibi, Laleh ^c   Azhdarzadeh, Morteza ^c   Aghaverdi, Haniyeh ^d   Tehrani, Khadijeh H ^d   Lotfi, Mina ^c   Kehoe, Patrick G ^e   Sheidaei, Ali ^f   Ghasemian, Anoosheh ^b   Darzi, Ehsan Rezaei ^b   Mahmoodi, Ramin ^g   Mahmoudi, Morteza ^a,c,h  

^a PASTEUR INSTITUTE OF IRAN   (Iran)

^b TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^c TEHRAN UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^d ISLAMIC AZAD UNIVERSITY   (Iran)

^e UNIVERSITY OF BRISTOL   (United Kingdom)

^f SHAHID BEHESHTI UNIVERSITY OF MEDICAL SCIENCES   (Iran)

^g INTERNATIONAL NEUROSCIENCE INSTITUTE   (Germany)

^h STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

Alzheimer's disease; amyloid pathology; cellular integrity; chronic conditions; lifestyle; multivalent cations homeostasis; risk factors

Indexed keywords

AMYLOID BETA PROTEIN; CATION; MULTIVALENT CATION; UNCLASSIFIED DRUG; BIOLOGICAL MARKER;

ALZHEIMER DISEASE; APOPTOSIS; ARTICLE; AUTOPHAGY; BLOOD BRAIN BARRIER; CALORIC INTAKE; DEPRESSION; DIABETES MELLITUS; HOMEOSTASIS; HUMAN; HYPERTENSION; INSOMNIA; IRON DEFICIENCY ANEMIA; NONHUMAN; OBESITY; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN FUNCTION; RISK FACTOR; ANIMAL; CLINICAL TRIAL (TOPIC); METABOLISM; PATHOPHYSIOLOGY;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BIOLOGICAL MARKERS; CATIONS; CLINICAL TRIALS AS TOPIC; HOMEOSTASIS; HUMANS;

EID: 84923211315     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-140321     Document Type: Article

References (191)

1. Abbott A (2011) Dementia: A problem for our age. Nature 475, S2-S4.
2. Brookmeyer R, Evans DA, Hebert L, Langa KM, Heeringa SG, Plassman BL, Kukull WA (2011) National estimates of the prevalence of Alzheimer's disease in the United States. Alzheimers Dement 7, 61-73.
3. Okie S (2011) Confronting Alzheimer's disease. N Engl J Med 365, 1069-1072.
4. Ballard C, Gauthier S, Corbett A, Brayne C, Aarsland D, JonesE(2011) Alzheimer's disease. Lancet 377, 1019-1031.
5. Ittner LM, Götz J (2010) Amyloid-β and tau - a toxic pas de deux in Alzheimer's disease. Nat Rev Neurosci 12, 67-72.
6. Chalmers KA, Wilcock GK, Love S (2004) Cortical Aβ, cerebral amyloid angiopathy and white matter changes in Alzheimer's disease. Neuropathol Appl Neurobiol 30, 207-208.
7. Kehoe PG, Passmore PA (2012) The renin-angiotensin system and antihypertensive drugs in Alzheimer's disease: Current standing of the angiotensin hypothesis? J Alzheimers Dis 30, S251-S268.
8. Dobson CM (2003) Protein folding and misfolding. Nature 426, 884-890.
9. Ghavami M, Rezaei M, Ejtehadi R, Lotfi M, Shokrgozar MA, Abd Emamy B, Raush J, Mahmoudi M (2012) Physiological temperature has a crucial role in amyloid beta in the absence and presence of hydrophobic and hydrophilic nanoparticles. ACS Chem Neurosci 4, 375-378.
10. Mahmoudi M, Kalhor HR, Laurent S, Lynch I (2013) Protein fibrillation and nanoparticle interactions: Opportunities and challenges. Nanoscale 5, 2570-2588.
11. Selkoe DJ (2004) Cell biology of protein misfolding: The examples of Alzheimer's and Parkinson's diseases. Nat Cell Biol 6, 1054-1061.
12. Haass C, Selkoe DJ (2007) Soluble protein oligomers in neurodegeneration: Lessons from the Alzheimer's amyloid β-peptide. Nat Rev Mol Cell Biol 8, 101-112.
13. Hamley I (2012) The amyloid beta peptide: A chemist's perspective. Role in Alzheimer's and fibrillization. Chem Rev 112, 5147-5192.
14. Mangialasche F, Solomon A, Winblad B, Mecocci P, Kivipelto M (2010) Alzheimer's disease: Clinical trials and drug development. Lancet Neurol 9, 702-716.
15. Masters CL, Selkoe DJ (2012) Biochemistry of amyloid β- protein and amyloid deposits in Alzheimer disease. Cold Spring Harb Perspect Med 2, a006262.
16. Mucke L, Selkoe DJ (2012) Neurotoxicity of amyloid β- protein: Synaptic and network dysfunction. Cold Spring Harb Perspect Med 2, a006338.
17. Gravitz L (2011) Drugs: A tangled web of targets. Nature 475, S9-S11.
18. Barakos J, Sperling R, Salloway S, Jack C, Gass A, Fiebach J, Tampieri D, Melançon D, Miaux Y, Rippon G (2013) MR imaging features of amyloid-related imaging abnormalities. Am J Neuroradiol 34, 1958-1965.
19. Selkoe DJ (2011) Resolving controversies on the path to Alzheimer's therapeutics. Nat Med 17, 1060-1065.
20. Bateman RJ, Xiong C, Benzinger TL, Fagan AM, Goate A, Fox NC, Marcus DS, Cairns NJ, Xie X, Blazey TM (2012) Clinical and biomarker changes in dominantly inherited Alzheimer's disease. N Engl J Med 367, 795-804.
21. Lannfelt L, Blennow K, Zetterberg H, Batsman S, Ames D, Harrison J, Masters CL, Targum S, Bush AI, Murdoch R, Wilson J, Ritchie CW(2008) Safety, efficacy, and biomarker findings of PBT2 in targeting Aβ as a modifying therapy for Alzheimer's disease:Aphase IIa, double-blind, randomised, placebo-controlled trial. Lancet Neurol 7, 779-786.
22. Faux NG, Ritchie CW, Gunn A, Rembach A, Tsatsanis A, Bedo J, Harrison J, Lannfelt L, Blennow K, Zetterberg H (2010) PBT2 rapidly improves cognition in Alzheimer's Disease: Additional phase II analyses. J Alzheimers Dis 20, 509-516.
23. Bush AI, Tanzi RE (2008) Therapeutics for Alzheimer's disease based on the metal hypothesis. Neurotherapeutics 5, 421-432.
24. Wesson DW, Levy E, Nixon RA, Wilson DA (2010) Olfactory dysfunction correlates with amyloid-β burden in an Alzheimer's disease mouse model. J Neurosci 30, 505-514.
25. Wang J, Luthey-Schulten ZA, Suslick KS (2003) Is the olfactory receptor a metalloprotein? Proc Natl Acad Sci U S A 100, 3035-3039.
26. Peters JM, Hummel T, Kratzsch T, Lötsch J, Skarke C, Frölich L (2003) Olfactory function in mild cognitive impairment and Alzheimer's disease: An investigation using psychophysical and electrophysiological techniques. Am J Psychiat 160, 1995-2002.
27. Wesson DW, WilsonD A, Nixon RA(2010) Should olfactory dysfunction be used as a biomarker of Alzheimer's disease? Expert Rev Neurother 10, 633-635.
28. Mahmoudi M, Suslick KS (2012) Protein fibrillation and the olfactory system: Speculations on their linkage. Trends Biotechnol 30, 609-610.
29. Krol S, Macrez R, Docagne F, Defer G, Laurent S, Rahman M, Hajipour MJ, Kehoe PG, MahmoudiM(2012) Therapeutic benefits from nanoparticles: The potential significance of nanoscience in diseases with compromise to the blood brain barrier. Chem Rev 113, 1877-1903.
30. Laurent S, Ejtehadi MR, Rezaei M, Kehoe PG, Mahmoudi M (2012) Interdisciplinary challenges and promising theranostic effects of nanoscience in Alzheimer's disease. RSC Adv 2, 5008-5033.
31. Bonda DJ, Lee HG, Blair JA, Zhu X, Perry G, Smith MA (2011) Role of metal dyshomeostasis in Alzheimer's disease. Metallomics 3, 267-270.
32. Andreini C, Cavallaro G, Lorenzini S, Rosato A (2013) MetalPDB: A database of metal sites in biological macromolecular structures. Nucleic Acids Res 41, D312-D319.
33. Witton J, Brown JT, Jones MW, Randall AD (2010) Altered synaptic plasticity in the mossy fibre pathway of transgenic mice expressing mutant amyloid precursor protein. Mol Brain 3, 32-39.
34. Bliss T, Collingridge G, Morris R (2014) Synaptic plasticity in health and disease: Introduction and overview. Philos Trans R Soc Lond B Biol Sci 369, 20130129.
35. Amadoro G, Calissano P (2011) Zinc, copper, neurotrophic factors and neurodegeneration. In Neurodegeneration: Metallostasis and Proteostasis. The Royal Society of Chemistry, pp. 141-151.
36. Duce JA, Bush AI (2010) Biological metals and Alzheimer's disease: Implications for therapeutics and diagnostics. Prog Neurobiol 92, 1-18.
37. Johnstone E, Chaney M, Norris F, Pascual R, Little S (1991) Conservation of the sequence of the Alzheimer's disease amyloid peptide in dog, polar bear and five other mammals by cross-species polymerase chain reaction analysis. Mol Brain Res 10, 299-305.
38. Greenough MA, Camakaris J, Bush AI (2013) Metal dyshomeostasis and oxidative stress in Alzheimer's disease. Neurochem Int 62, 540-555.
39. Alic N, Partridge L (2011) Death and dessert: Nutrient signalling pathways and ageing. Current Opin Cell Biol 23, 738-743.
40. Conn CS, Qian SB (2013) Nutrient signaling in protein homeostasis: An increase in quantity at the expense of quality. Sci Signal 6, ra24-ra24.
41. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153, 1194-1217.
42. Drakesmith H, Prentice AM (2012) Hepcidin and the ironinfection axis. Science 338, 768-772.
43. Saibil HR (2013) Machinery to reverse irreversible aggregates. Science 339, 1040-1041.
44. Hartl FU, Bracher A, Hayer-Hartl M (2011) Molecular chaperones in protein folding and proteostasis. Nature 475, 324-332.
45. Seliger SL, Siscovick DS, Stehman-Breen CO, Gillen DL, Fitzpatrick A, Bleyer A, Kuller LH (2004) Moderate renal impairment and risk of dementia among older adults: The cardiovascular health cognition study. J Am Soc Nephrol 15, 1904-1911.
46. Yaffe K, Ackerson L, Tamura MK, Le Blanc P, Kusek JW, Sehgal AR, Cohen D, Anderson C, Appel L, DeSalvo K (2010) Chronic kidney disease and cognitive function in older adults: Findings from the chronic renal insufficiency cohort cognitive study. J Am Geriatr Soc 58, 338-345.
47. Zhang G, Li J, Purkayastha S, Tang Y, Zhang H, Yin Y, Li B, Liu G, Cai D (2013) Hypothalamic programming of systemic ageing involving IKK-β, NF-κB and GnRH. Nature 497, 211-216.
48. Atwood CS, Meethal SV, Liu T, Wilson AC, Gallego M, Smith MA, Bowen RL (2005) Dysregulation of the hypothalamic-pituitary-gonadal axis with menopause and andropause promotes neurodegenerative senescence. J Neuropathol Exp Neurol 64, 93-103.
49. Mines MA, Beurel E, Jope RS (2011) Regulation of cell survival mechanisms in Alzheimer's disease by glycogen synthase kinase-3. Int J Alzheimers Dis 2011, 861072.
50. Yoon SO, Park DJ, Ryu JC, Ozer HG, Tep C, Shin YJ, Lim TH, Pastorino L, Kunwar AJ, Walton JC (2012) JNK3 perpetuates metabolic stress induced by Aβ peptides. Neuron 75, 824-837.
51. Wang S, Wu J, Nie S- D, Bereczki E, Pei J-J (2013) Dysregulated mTOR-dependent signaling in neurodegeneration or carcinogenesis: Implication for Alzheimer's disease and brain tumors. J Alzheimers Dis 37, 495-505.
52. Johnson SC, Rabinovitch PS, Kaeberlein M (2013) mTOR is a key modulator of ageing and age-related disease. Nature 493, 338-345.
53. Jung CH, Ro S- H, Cao J, Otto NM, Kim D-H (2010) mTOR regulation of autophagy. FEBS Lett 584, 1287-1295.
54. Nixon RA, Yang D-S (2012) Autophagy and neuronal cell death in neurological disorders. Cold Spring Harb Perspect Biol 4, a008839.
55. Yang Y, Coleman M, Zhang L, Zheng X, Yue Z (2013) Autophagy in axonal and dendritic degeneration. Trends Neurosci 36, 418-428.
56. García-Lara J, Aguilar-Navarro S, Gutiérrez-Robledo LM, Ávila-Funes JA (2010) The metabolic syndrome, diabetes, and Alzheimer's disease. Rev Invest Clin 62, 343-349.
57. Bredesen DE, John V (2013) Next generation therapeutics for Alzheimer's disease. EMBO Mol Med 5, 795-798.
58. Chang H- C, Guarente L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153, 1448-1460.
59. Coffman TM (2011) Under pressure: The search for the essential mechanisms of hypertension. Nat Med 17, 1402-1409.
60. Wilson AC, Clemente L, Liu T, Bowen RL, Meethal SV, Atwood CS (2008) Reproductive hormones regulate the selective permeability of the blood-brain barrier. Biochim Biophys Acta 1782, 401-407.
61. Rodin J (1985) Insulin levels, hunger, and food intake: An example of feedback loops in body weight regulation. Health Psychol 4, 1-24.
62. Schwartz MW, Seeley RJ, Tschöp MH, Woods SC, Morton GJ, Myers MG, D'Alessio D (2013) Cooperation between brain and islet in glucose homeostasis and diabetes. Nature 503, 59-66.
63. Chang L, Chiang S- H, Saltiel AR (2004) Insulin signaling and the regulation of glucose transport. Mol Med 10, 65-71.
64. Fernandez AM, Torres-Alemán I (2012) The many faces of insulin-like peptide signalling in the brain. Nat Rev Neurosci 13, 225-239.
65. Banks WA (2004) The source of cerebral insulin. Eur J Pharmacol 490, 5-12.
66. Candeias E, Duarte AI, Carvalho C, Correia SC, Cardoso S, Santos RX, Plácido AI, Perry G, Moreira PI (2012) The impairment of insulin signaling in Alzheimer's disease. IUBMB Life 64, 951-957.
67. Schwartz MW, Figlewicz DP, Baskin DG, Woods SC, Porte D(1992) Insulin in the brain:Ahormonal regulator of energy balance. Endocrine Rev 13, 387-414.
68. Zhao J, Brault JJ, Schild A, Goldberg AL (2008) Coordinate activation of autophagy and the proteasome pathway by FoxO transcription factor. Autophagy 4, 378-380.
69. Lilienbaum A (2013) Relationship between the proteasomal system and autophagy. Int J Biochem Mol Biol 4, 1-26.
70. Zhou J, Liao W, Yang J, Ma K, Li X, Wang Y, Wang D, Wang L, Zhang Y, Yin Y (2012) FOXO3 induces FOXO1- dependent autophagy by activating the AKT1 signaling pathway. Autophagy 8, 0-11.
71. Pivtoraiko VN, Stone SL, Roth KA, Shacka JJ (2009) Oxidative stress and autophagy in the regulation of lysosome-dependent neuron death. Antioxid Redox Signal 11, 481-496.
72. Horowitz MP, Greenamyre JT (2010) Mitochondrial iron metabolism and its role in neurodegeneration. J Alzheimers Dis 20, 551-568.
73. Ecker DJ, Butt T, Sternberg E, Neeper M, Debouck C, Gorman J, Crooke S (1986) Yeast metallothionein function in metal ion detoxification. J Biol Chem 261, 16895-16900.
74. Kurz T, Terman A, Gustafsson B, Brunk UT (2008) Lysosomes in iron metabolism, ageing and apoptosis. Histochem Cell Biol 129, 389-406.
75. Niswender KD, Morton GJ, Stearns WH, Rhodes CJ, Myers MG, Schwartz MW (2001) Intracellular signalling: Key enzyme in leptin-induced anorexia. Nature 413, 794-795.
76. Banks WA (2004) The many lives of leptin. Peptides 25, 331-338.
77. Foster M, Samman S (2010) Zinc and redox signaling: Perturbations associated with cardiovascular disease and diabetes mellitus. Antioxid Redox Signal 13, 1549-1573.
78. Woods SC, Seeley RJ (2000) Adiposity signals and the control of energy homeostasis. Nutrition 16, 894-902.
79. Varela L, Horvath TL (2012) Leptin and insulin pathways in POMC and AgRP neurons that modulate energy balance and glucose homeostasis. EMBO Rep 13, 1079-1086.
80. Rao J, Keleshian V, Klein S, Rapoport S (2012) Epigenetic modifications in frontal cortex from Alzheimer's disease and bipolar disorder patients. Transl Psychiatry 2, e132.
81. Schrötter A, Pfeiffer K, El Magraoui F, Platta HW, Erdmann R, Meyer HE, Egensperger R, Marcus K, Müller T (2012) The Amyloid precursor protein (APP) family members are key players in S-adenosylmethionine formation by MAT2A and modify BACE1 and PSEN1 gene expressionrelevance for Alzheimer's disease. Mol Cell Proteomics 11, 1274-1288.
82. Bakulski KM, Dolinoy DC, Sartor MA, Paulson HL, Konen JR, Lieberman AP, Albin RL, Hu H, Rozek LS (2012) Genome-wide DNA methylation differences between lateonset Alzheimer's disease and cognitively normal controls in human frontal cortex. J Alzheimers Dis 29, 571-588.
83. Medici V, Shibata NM, Kharbanda KK, LaSalle JM, Woods R, Liu S, Engelberg JA, Devaraj S, Török NJ, Jiang JX (2013)Wilson's disease: Changes in methionine metabolism and inflammation affect global DNA methylation in early liver disease. Hepatology 57, 555-565.
84. Tajuddin SM, Amaral AF, FernándezA F, Rodríguez-Rodero S, Rodríguez RM, Moore LE, Tardón A, Carrato A, García- Closas M, Silverman DT (2013) Genetic and non-genetic predictors of LINE-1 methylation in leukocyte DNA. Environ Health Perspect 121, 650-656.
85. Perng W, Rozek LS, Mora-Plazas M, Duchin O, Marin C, Forero Y, Baylin A, Villamor E (2012) Micronutrient status and global DNA methylation in school-age children. Epigenetics 7, 1133-1141.
86. Koturbash I, Simpson NE, Beland FA, Pogribny IP (2012) Alterations in histone H4 lysine 20 methylation: Implications for cancer detection and prevention. Antioxid Redox Signal 17, 365-374.
87. Tian X, Diaz F (2013) Acute dietary zinc deficiency before conception compromises oocyte epigenetic programming and disrupts embryonic development. Dev Biol 376, 51-61.
88. Salminen A, Kaarniranta K (2012) AMP-activated protein kinase (AMPK) controls the aging process via an integrated signaling network. Ageing Res Rev 11, 230-241.
89. Trepanowski JF, Canale RE, Marshall KE, Kabir MM, Bloomer RJ (2011) Impact of caloric and dietary restriction regimens on markers of health and longevity in humans and animals: A summary of available findings. Nutr J 10, 1-13.
90. Omodei D, Fontana L (2011) Calorie restriction and prevention of age-associated chronic disease. FEBS Lett 585, 1537-1542.
91. Fontana L (2009) The scientific basis of caloric restriction leading to longer life. Curr Opin Gastroenterol 25, 144-150.
92. Hands SL, Proud CG, Wyttenbach A (2009) mTOR's role in ageing: Protein synthesis or autophagy? Aging 1, 586-597.
93. Dröge W, Schipper HM(2007) Oxidative stress and aberrant signaling in aging and cognitive decline. Aging Cell 6, 361-370.
94. Pang WW, Schrier SL (2012) Anemia in the elderly. Curr Opin Hematol 19, 133-140.
95. Kau AL, Ahern PP, Griffin NW, Goodman AL, Gordon JI (2011) Human nutrition, the gut microbiome and the immune system. Nature 474, 327-336.
96. Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124, 471-484.
97. Fretham SJ, Carlson ES, Georgieff MK (2011) The role of iron in learning and memory. Adv Nutr 2, 112-121.
98. Bayeva M, Khechaduri A, Puig S, Chang H- C, Patial S, Blackshear PJ, Ardehali H (2012) mTOR regulates cellular iron homeostasis through Tristetraprolin. Cell Metab 16, 645-657.
99. Levine B, Kroemer G (2009) Autophagy in aging, disease and death: The true identity of a cell death impostor. Cell Death Differ 16, 1-2.
100. Nixon RA, Yang D-S (2011) Autophagy failure in Alzheimer's disease - locating the primary defect. Neurobiol Dis 43, 38-45.
101. Mills E, Dong X-p, Wang F, Xu H (2010) Mechanisms of brain iron transport: Insight into neurodegeneration and CNS disorders. Future Med Chem 2, 51-64.
102. Rouault TA (2013) Iron metabolism in the CNS: Implications for neurodegenerative diseases. Nat Rev Neurosci 14, 551-564.
103. Kurz T, Eaton JW, Brunk UT (2010) Redox activity within the lysosomal compartment: Implications for aging and apoptosis. Antioxid Redox Signal 13, 511-523.
104. Kaiyala KJ, Prigeon RL, Kahn SE, Woods SC, Schwartz MW(2000) Obesity induced by a high-fat diet is associated with reduced brain insulin transport in dogs. Diabetes 49, 1525-1533.
105. Israel P, Park CR, Schwartz M, Green P, Sipols A, Woods S, Porte D, Figlewicz D (1993) Effect of diet-induced obesity and experimental hyperinsulinemia on insulin uptake into CSF of the rat. Brain Res Bull 30, 571-575.
106. Parrella E, Maxim T, Maialetti F, Zhang L, Wan J, Wei M, Cohen P, Fontana L, Longo VD (2013) Protein restriction cycles reduce IGF-1 and phosphorylated Tau, and improve behavioral performance in an Alzheimer's disease mouse model. Aging Cell 12, 257-268.
107. Collino M, Aragno M, Castiglia S, Tomasinelli C, Thiemermann C, Boccuzzi G, Fantozzi R (2009) Insulin reduces cerebral ischemia/reperfusion injury in the hippocampus of diabetic rats a role for glycogen synthase kinase-3β. Diabetes 58, 235-242.
108. Settembre C, Di Malta C, Polito VA, Arencibia MG, Vetrini F, Erdin S, Erdin SU, Huynh T, Medina D, Colella P (2011) TFEB links autophagy to lysosomal biogenesis. Sci Signal 332, 1429-1433.
109. Craft S (2007) Insulin resistance and Alzheimer's disease pathogenesis: Potential mechanisms and implications for treatment. Curr Alzheimer Res 4, 147-152.
110. Frölich L, Blum-Degen D, Bernstein H- G, Engelsberger S, Humrich J, Laufer S, Muschner D, Thalheimer A, Türk A, Hoyer S (1998) Brain insulin and insulin receptors in aging and sporadic Alzheimer's disease. J Neural Transm 105, 423-438.
111. Hoyer S (2002) 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, 991-1002.
112. Luchsinger JA, Gustafson DR (2009) Adiposity and Alzheimer's disease. Curr Opin Clin Nutr Metab Care 12, 15-21.
113. Talbot K, Wang HY, Kazi H (2012) Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. J Clin Invest 122, 1316-1338.
114. Lucas JJ, Hernandez F, Gomez-Ramos P, Moran MA, Hen R, Avila J (2001) Decreased nuclear [beta]-catenin, tau hyperphosphorylation and neurodegeneration in GSK- 3[beta] conditional transgenic mice. EMBO J 20, 27-39.
115. Hanger DP, Hughes K, Woodgett JR, Brion J- P, Anderton BH(1992) Glycogen synthase kinase-3 induces Alzheimer's disease-like phosphorylation of tau: Generation of paired helical filament epitopes and neuronal localisation of the kinase. Neurosci Lett 147, 58-62.
116. Mandelkow E- M, Drewes G, Biernat J, Gustke N, Van Lint J, Vandenheede Jv,MandelkowE (1992) Glycogen synthase kinase-3 and the Alzheimer-like state of microtubuleassociated protein tau. FEBS Lett 314, 315-321.
117. Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40, 405-412.
118. Wolff S (1993) Diabetes mellitus and free radicals Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br Med Bull 49, 642-652.
119. Gispen WH, Biessels G-J (2000) Cognition and synaptic plasticity in diabetes mellitus. Trends Neurosci 23, 542-549.
120. Stranahan AM, Arumugam TV, Cutler RG, Lee K, Egan JM, Mattson MP (2008) Diabetes impairs hippocampal function through glucocorticoid-mediated effects on new and mature neurons. Nat Neurosci 11, 309-317.
121. De Kloet ER, Vreugdenhil E, Oitzl MS, Jöels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19, 269-301.
122. Craft S, ChristenY(2010) Diabetes, Insulin and Alzheimer's Disease, Springer-Verlag Berlin Heidelberg.
123. Lee HB, Lyketsos CG (2003) Depression in Alzheimer's disease: Heterogeneity and related issues. Biol Psychiat 54, 353-362.
124. Kessing LV (2012) Depression and the risk for dementia. Curr Opin Psychiatry 25, 457-461.
125. Lyketsos CG, Olin J (2002) Depression in Alzheimer's disease: Overview and treatment. Biol Psychiat 52, 243-252.
126. Rubin RT, Poland RE, Lesser IM, Winston RA, Blodgett A (1987) Neuroendocrine aspects of primary endogenous depression: I. Cortisol secretory dynamics in patients and matched controls. Arch Gen Psychiatry 44, 328.
127. Nemeroff CB, Widerlov E, Bissette G, Walleus H, Karlsson I, Eklund K, Kilts CD, Loosen PT, Vale W (1984) Elevated concentrations of CSF corticotropin-releasing factor-like immunoreactivity in depressed patients. Science 226, 1342-1344.
128. Steckler T, Holsboer F, Reul JM (1999) Glucocorticoids and depression. Baillieres Best Pract Res Clin Endocrinol Metab 13, 597-614.
129. Holsboer F (2000) The corticosteroid receptor hypothesis of depression. Neuropsychopharmacology 23, 477-501.
130. Shimizu N, Yoshikawa N, Ito N, Maruyama T, Suzuki Y, Takeda S-i, Nakae J, Tagata Y, Nishitani S, Takehana K (2011) Crosstalk between glucocorticoid receptor and nutritional sensor mTOR in skeletal muscle. Cell Metab 13, 170-182.
131. Polman JA E, Hunter RG, Speksnijder N, van den Oever JM, Korobko OB, McEwen BS, de Kloet ER, Datson NA (2012) Glucocorticoids modulate the mTOR pathway in the hippocampus: Differential effects depending on stress history. Endocrinology 153, 4317-4327.
132. Miller AL, Garza AS, Johnson BH, Thompson EB (2007) Pathway interactions between MAPKs, mTOR, PKA, and the glucocorticoid receptor in lymphoid cells. Cancer Cell Int 7, 3.
133. Osorio RS, Pirraglia E, Agüera-Ortiz LF, During EH, Sacks H, Ayappa I, Walsleben J, Mooney A, Hussain A, Glodzik L (2011) Greater risk of Alzheimer's disease in older adults with insomnia. J Am Geriatr Soc 59, 559-562.
134. Spira AP, Gamaldo AA, An Y, Wu MN, Simonsick EM, Bilgel M, Zhou Y, Wong DF, Ferrucci L, Resnick SM (2013) Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol 70, 1537-1543.
135. Lim AS, Yu L, Kowgier M, Schneider JA, Buchman AS, Bennett DA (2013) Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurol 70, 1544-1551.
136. Ju Ye, McLeland JS, Toedebusch CD, Xiong C, Fagan AM, Duntley SP, Morris JC, Holtzman DM (2013) Sleep quality and preclinical Alzheimer disease. JAMA Neurol 70, 587-593.
137. Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, O'Donnell J, Christensen DJ, Nicholson C, Iliff JJ (2013) Sleep drives metabolite clearance from the adult brain. Science 342, 373-377.
138. Vgontzas AN, Chrousos GP (2002) Sleep, the hypothalamic-pituitary-adrenal axis, and cytokines: Multiple interactions and disturbances in sleep disorders. Endocrinol Metab Clin North Am 31, 15-36.
139. Chrousos GP, KinoT(2007) Glucocorticoid action networks and complex psychiatric and/or somatic disorders. Stress 10, 213-219.
140. Chrousos GP, Kino T (2009) Glucocorticoid signaling in the cell. Ann N Y Acad Sci 1179, 153-166.
141. Roth T, Roehrs T, Pies R (2007) Insomnia: Pathophysiology and implications for treatment. Sleep Med Rev 11, 71-79.
142. Riemann D, Kloepfer C, Berger M (2009) Functional and structural brain alterations in insomnia: Implications for pathophysiology. Eur J Neurosci 29, 1754-1760.
143. Roth T (2007) Insomnia: Definition, prevalence, etiology, and consequences. J Clin Sleep Med 3, S7-S10.
144. Vgontzas AN, Bixler EO, Lin H- M, Prolo P, Mastorakos G, Vela-Bueno A, Kales A, Chrousos GP (2001) Chronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: Clinical implications. J Clin Endocr Metab 86, 3787-3794.
145. Tevy MF, Giebultowicz J, Pincus Z, Mazzoccoli G, Vinciguerra M (2013) Aging signaling pathways and circadian clock-dependent metabolic derangements. Trends Endocrinol Metab 24, 229-237.
146. Lee Y, Montell C (2013) Drosophila TRPA1 functions in temperature control of circadian rhythm in pacemaker neurons. J Neurosci 33, 6716-6725.
147. Xiao R, Zhang B, Dong Y, Gong J, Xu T, Liu J, Xu X (2013) A genetic program promotes C. elegans longevity at cold temperatures via a thermosensitive TRP channel. Cell 152, 806-817.
148. Ostchega Y, Yoon SS, Hughes J, Louis T (2008) Hypertension awareness, treatment, and control-continued disparities in adults: United States, 2005-2006. NCHS data brief, 1-8.
149. Heistad DD, Marcus ML (1979) Effect of sympathetic stimulation on permeability of the blood-brain barrier to albumin during acute hypertension in cats. Circ Res 45, 331-338.
150. Mueller SM, Heistad DD (1980) Effect of chronic hypertension on the blood-brain barrier. Hypertension 2, 809-812.
151. Paton JR, Wang S, Polson J, Kasparov S (2008) Signalling across the blood brain barrier by angiotensin II: Novel implications for neurogenic hypertension. J Mol Med 86, 705-710.
152. Mayhan WG (1990) Disruption of blood-brain barrier during acute hypertension in adult and aged rats. Am J Physiol 258, H1735-H1738.
153. Mayhan WG(1995) Role of nitric oxide in disruption of the blood-brain barrier during acute hypertension. Brain Res 686, 99-103.
154. Nava E, Rodriguez F, Moreno C, Llinas M, Salazar F (2000) Release of nitric oxide after acute hypertension. J Cardiovasc Pharmacol 36, 444-450.
155. Zalba G, San José G, Moreno MU, Fortuño MA, Fortuño A, Beaumont FJ, Díez J (2001) Oxidative stress in arterial hypertension role of NAD (P) H oxidase. Hypertension 38, 1395-1399.
156. Zimmerman MC, Lazartigues E, Sharma RV, Davisson RL (2004) Hypertension caused by angiotensin II infusion involves increased superoxide production in the central nervous system. Circ Res 95, 210-216.
157. Poulet R, Gentile MT, Vecchione C, Distaso M, Aretini A, Fratta L, Russo G, Echart C, Maffei A, De Simoni MG (2005) Acute hypertension induces oxidative stress in brain tissues. J Cereb Blood Flow Metab 26, 253-262.
158. Davies PF, Rennke HG, Cotran RS (1981) Influence of molecular charge upon the endocytosis and intracellular fate of peroxidase activity in cultured arterial endothelium. J Cell Sci 49, 69-86.
159. Pelikan P, Gimbrone MA, Cotran RS (1979) Distribution andmovement of anionic cell surface sites in cultured human vascular endothelial cells. Atherosclerosis 32, 69-80.
160. Mayhan WG, Faraci FM, Siems JL, Heistad DD(1989) Role of molecular charge in disruption of the blood-brain barrier during acute hypertension. Circ Res 64, 658-664.
161. Mueller SM, Luft FC (1982) The blood-brain barrier in renovascular hypertension. Stroke 13, 229-234.
162. Tang J-p, Xu Z- Q, Douglas FL, Rakhit A, Melethil S (1993) Increased blood-brain barrier permeability of amino acids in chronic hypertension. Life Sci 53, PL417-PL420.
163. Launer LJ, Ross GW, Petrovitch H, Masaki K, Foley D, White LR, Havlik RJ (2000) Midlife blood pressure and dementia: The Honolulu-Asia aging study. Neurobiol Aging 21, 49-55.
164. Skoog I, Nilsson L, Persson G, Lernfelt B, Landahl S, Palmertz B, Andreasson L, Oden A, Svanborg A (1996) 15-year longitudinal study of blood pressure and dementia. Lancet 347, 1141-1145.
165. Morris MC, Scherr PA, Hebert LE, Glynn RJ, Bennett DA, Evans DA(2001) Association of incident Alzheimer disease and blood pressure measured from 13 years before to 2 years after diagnosis in a large community study. Arch Neurol 58, 1640-1646.
166. Sparks DL (1997) Coronary artery disease, hypertension, Apo E, and cholesterol: A link to Alzheimer's disease? Ann N Y Acad Sci 826, 128-146.
167. Launer LJ, Masaki K, Petrovitch H, Foley D, Havlik RJ (1995) The association between midlife blood pressure levels and late-life cognitive function. JAMA 274, 1846-1851.
168. Kilander L, Nyman H, Boberg M, Hansson L, Lithell H (1998) Hypertension is related to cognitive impairment a 20-year follow-up of 999 men. Hypertension 31, 780-786.
169. Tzourio C, Dufouil C, Ducimetiere P, Alpérovitch A (1999) Cognitive decline in individuals with high blood pressure A longitudinal study in the elderly. Neurology 53, 1948-1948.
170. Gentile MT, Poulet R, Pardo AD, Cifelli G, Maffei A, Vecchione C, Passarelli F, Landolfi A, Carullo P, Lembo G (2009) β-amyloid deposition in brain is enhanced in mouse models of arterial hypertension. Neurobiol Aging 30, 222-228.
171. Power MC, Weuve J, Gagne JJ, McQueen MB, Viswanathan A, BlackerD(2011) The association between blood pressure and incident Alzheimer disease: A systematic review and meta-analysis. Epidemiology 22, 646-659.
172. Ashby El, Kehoe PG (2013) Current status of renin-aldosterone angiotensin system-targeting antihypertensive drugs as therapeutic options for Alzheimer's disease. Expert Opin Investig Drugs 22, 1229-1242.
173. Kehoe PG, Davies NM, Martin RM, Ben-Shlomo Y (2013) Associations of angiotensin targeting antihypertensive drugs with mortality and hospitalization in primary care patients with dementia. J Alzheimers Dis 33, 999-1008.
174. Goodison WV, Frisardi V, Kehoe PG (2012) Calcium channel blockers and Alzheimer's disease: Potential relevance in treatment strategies of metabolic syndrome. J Alzheimers Dis 30, S269-S282.
175. Li N- C, Lee A, Whitmer RA, Kivipelto M, Lawler E, Kazis LE, Wolozin B (2010) Use of angiotensin receptor blockers and risk of dementia in a predominantly male population: Prospective cohort analysis. Brit Med J 340, b5465.
176. Gao Y, O'Caoimh R, Healy L, Kerins DM, Eustace J, Guyatt G, Sammon D, Molloy DW(2013) Effects of centrally acting ACE inhibitors on the rate of cognitive decline in dementia. BMJ Open 3, e002881.
177. Matter K, Balda MS (2003) Signalling to and from tight junctions. Nat Rev Mol Cell Biol 4, 225-237.
178. Shan Z, Zubcevic J, Shi P, Jun JY, Dong Y, Murça TM, Lamont GJ, Cuadra A, Yuan W, QiY(2013) Chronic knockdown of the nucleus of the solitary tract AT1 receptors increases blood inflammatory-endothelial progenitor cell ratio and exacerbates hypertension in the spontaneously hypertensive rat. Hypertension 61, 1328-1333.
179. Collaboration GC (2013) GBD 2010 country results: A global public good. Lancet 381, 965-970.
180. Murray CJ, Vos T, Lozano R, Naghavi M, Flaxman AD, Michaud C, Ezzati M, Shibuya K, Salomon JA, Abdalla S (2013) Disability-adjusted life years (DALYs) for 291 diseases and injuries in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2197-2223.
181. Lim SS, Vos T, Flaxman AD, Danaei G, Shibuya K, Adair- Rohani H, Amann M, Anderson HR, Andrews KG, Aryee M (2013) A comparative risk assessment of burden of disease and injury attributable to 67 risk factors and risk factor clusters in 21 regions, 1990-2010: A systematic analysis for the Global Burden of Disease Study 2010. Lancet 380, 2224-2260.
182. King G, Tomz M, Wittenberg J (2000) Making the most of statistical analyses: Improving interpretation and presentation. Am J Polit Sci 44, 347-361.
183. Folli F, Corradi D, Fanti P, Davalli A, Paez A, Giaccari A, Perego C, Muscogiuri G (2011) The role of oxidative stress in the pathogenesis of type 2 diabetes mellitus micro-and macrovascular complications: Avenues for a mechanisticbased therapeutic approach. Curr Diabetes Rev 7, 313-324.
184. Sankhla M, Sharma TK, Mathur K, Rathor JS, Butolia V, Gadhok AK, Vardey SK, Sinha M, Kaushik G (2011) Relationship of oxidative stress with obesity and its role in obesity induced metabolic syndrome. Clin Lab 58, 385-392.
185. Nagababu E, Gulyani S, Earley CJ, Cutler RG, Mattson MP, Rifkind JM (2008) Iron-deficiency anaemia enhances red blood cell oxidative stress. Free Radic Res 42, 824-829.
186. Akihiko N, Perry G, Aliev G, Hirai K, Takeda A, Balraj EK, Jones PK, Ghanbari H, Wataya T, Shimohama S, Chiba S, Atwood CS, Petersen RB, Smith MA(2001) Oxidative damage is the earliest event in Alzheimer disease. J Neuropath Exp Neur 60, 759-767.
187. Michel TM, Puelschen D, Thome J (2012) The role of oxidative stress in depressive disorders. Curr Pharm Design 18, 5890-5899.
188. Gulec M, Ozkol H, Selvi Y, Tuluce Y, Aydin A, Besiroglu L, Ozdemir PG(2012) Oxidative stress in patients with primary insomnia. Prog Neuro-Psychoph 37, 247-251.
189. Christen Y (2000) Oxidative stress and Alzheimer disease. Am J Clin Nutr 71, 621s-629s.
190. Perry G, Mondragón-Rodríguez S, Nunomura A, Zhu X, Moreira PI, Smith MA (2011) Oxidative stress and balance in neurodegenerative diseases. Neurodegeneration: The Molecular Pathology of Dementia and Movement Disorders, Second Edition, 10-12.
191. Lee D- H, Gold R, Linker RA (2012) Mechanisms of oxidative damage in multiple sclerosis and neurodegenerative diseases: Therapeutic modulation via fumaric acid esters. Int J Mol Sci 13, 11783-11803.