1. Selkoe DJ, Schenk D. Alzheimer's disease: molecular understanding predicts amyloid-based therapeutics. Annu Rev Pharmacol Toxicol. 2003; 43(1):545–584.
2. Brion JP, Anderton BH, Authelet M, Dayanandan R, Leroy K, Lovestone S, et al. Neurofibrillary tangles and tau phosphorylation. Biochem Soc Symp. 2001; 67(67):81–88.
3. Hardy J. Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 1997; 20(4):154–159.
4. Alzheimer's Association. 2012 Alzheimer's disease facts and figures. Alzheimers Dement. 2012; 8(2):131–168.
5. Piaceri I, Nacmias B, Sorbi S. Genetics of familial and sporadic Alzheimer's disease. Front Biosci (Elite Ed). 2013; 5(1):167–177.
6. Luchsinger JA, Tang MX, Shea S, Mayeux R. Hyperinsulinemia and risk of Alzheimer disease. Neurology. 2004; 63(7):1187–1192.
7. Mattson MP. Pathways towards and away from Alzheimer's disease. Nature. 2004; 430(7000):631–639.
8. Di Domenico F, Perluigi M, Butterfield DA, Cornelius C, Calabrese V. Oxidative damage in rat brain during aging: interplay between energy and metabolic key target proteins. Neurochem Res. 2010; 35(12):2184–2192.
9. Butterfield DA, Drake J, Pocernich C, Castegna A. Evidence of oxidative damage in Alzheimer's disease brain: central role for amyloid beta-peptide. Trends Mol Med. 2001; 7(12):548–554.
10. Unsal C, Oran M, Albayrak Y, Aktas C, Erboga M, Topcu B, et al. Neuroprotective effect of ebselen against intracerebroventricular streptozotocin-induced neuronal apoptosis and oxidative stress in rats. Toxicol Ind Health. 2016; 32(4):730–740.
11. Scheff SW, Sparks L, Price DA. Quantitative assessment of synaptic density in the entorhinal cortex in Alzheimer's disease. Ann Neurol. 1993; 34(3):356–361.
12. Wollen KA. Alzheimer's disease: the pros and cons of pharmaceutical, nutritional, botanical, and stimulatory therapies, with a discussion of treatment strategies from the perspective of patients and practitioners. Altern Med Rev. 2010; 15(3):223–244.
13. Rodríguez JJ, Jones VC, Tabuchi M, Allan SM, Knight EM, LaFerla FM, et al. Impaired adult neurogenesis in the dentate gyrus of a triple transgenic mouse model of Alzheimer's disease. PLoS One. 2008; 3(8):e2935.
14. Akter K, Lanza EA, Martin SA, Myronyuk N, Rua M, Raffa RB. Diabetes mellitus and Alzheimer's disease: shared pathology and treatment? Br J Clin Pharmacol. 2011; 71(3):365–376.
15. George-Hyslop PS, Rossor M. Alzheimer's disease. Unravelling the disease process. Lancet. 2001; 358:Suppl. S1.
16. Guerreiro RJ, Gustafson DR, Hardy J. The genetic architecture of Alzheimer's disease: beyond APP, PSENs and APOE. Neurobiol Aging. 2012; 33(3):437–456.
17. Polvikoski T, Sulkava R, Haltia M, Kainulainen K, Vuorio A, Verkkoniemi A, et al. Apolipoprotein E, dementia, and cortical deposition of beta-amyloid protein. N Engl J Med. 1995; 333(19):1242–1247.
18. Lorenzo A, Yankner BA. Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc Natl Acad Sci U S A. 1994; 91(25):12243–12247.
19. Cleary JP, Walsh DM, Hofmeister JJ, Shankar GM, Kuskowski MA, Selkoe DJ, et al. Natural oligomers of the amyloid-beta protein specifically disrupt cognitive function. Nat Neurosci. 2005; 8(1):79–84.
20. Song MS, Saavedra L, de Chaves EI. Apoptosis is secondary to non-apoptotic axonal degeneration in neurons exposed to Abeta in distal axons. Neurobiol Aging. 2006; 27(9):1224–1238.
21. Selkoe DJ. Resolving controversies on the path to Alzheimer's therapeutics. Nat Med. 2011; 17(9):1060–1065.
22. McLean CA, Cherny RA, Fraser FW, Fuller SJ, Smith MJ, Beyreuther K, et al. Soluble pool of Abeta amyloid as a determinant of severity of neurodegeneration in Alzheimer's disease. Ann Neurol. 1999; 46(6):860–866.
23. Gong Y, Chang L, Viola KL, Lacor PN, Lambert MP, Finch CE, et al. Alzheimer's disease-affected brain: presence of oligomeric A beta ligands (ADDLs) suggests a molecular basis for reversible memory loss. Proc Natl Acad Sci U S A. 2003; 100(18):10417–10422.
24. Lei M, Xu H, Li Z, Wang Z, O'hMalley TT, Zhang D, et al. Soluble Aβ oligomers impair hippocampal LTP by disrupting glutamatergic/GABAergic balance. Neurobiol Dis. 2016; 85:111–121.
25. Oakley H, Cole SL, Logan S, Maus E, Shao P, Craft J, et al. Intraneuronal beta-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J Neurosci. 2006; 26(40):10129–10140.
26. Smith WW, Gorospe M, Kusiak JW. Signaling mechanisms underlying Abeta toxicity: potential therapeutic targets for Alzheimer's disease. CNS Neurol Disord Drug Targets. 2006; 5(3):355–361.
27. Kuner P, Schubenel R, Hertel C. Beta-amyloid binds to p57NTR and activates NFkappaB in human neuroblastoma cells. J Neurosci Res. 1998; 54(6):798–804.
28. Yan SD, Chen X, Fu J, Chen M, Zhu H, Roher A, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature. 1996; 382(6593):685–691.
29. Wang HY, Lee DH, Davis CB, Shank RP. Amyloid peptide Abeta(1-42) binds selectively and with picomolar affinity to alpha7 nicotinic acetylcholine receptors. J Neurochem. 2000; 75(3):1155–1161.
30. Jhamandas JH, MacTavish D. Antagonist of the amylin receptor blocks beta-amyloid toxicity in rat cholinergic basal forebrain neurons. J Neurosci. 2004; 24(24):5579–5584.
31. Song MS, Rauw G, Baker GB, Kar S. Memantine protects rat cortical cultured neurons against beta-amyloid-induced toxicity by attenuating tau phosphorylation. Eur J Neurosci. 2008; 28(10):1989–2002.
32. Mattson MP, Chan SL. Neuronal and glial calcium signaling in Alzheimer's disease. Cell Calcium. 2003; 34(4-5):385–397.
33. Blurton-Jones M, Laferla FM. Pathways by which Abeta facilitates tau pathology. Curr Alzheimer Res. 2006; 3(5):437–448.
34. Bi X, Gall CM, Zhou J, Lynch G. Uptake and pathogenic effects of amyloid beta peptide 1-42 are enhanced by integrin antagonists and blocked by NMDA receptor antagonists. Neuroscience. 2002; 112(4):827–840.
35. Nagele RG, D'Andrea MR, Anderson WJ, Wang HY. Intracellular accumulation of beta-amyloid(1-42) in neurons is facilitated by the alpha 7 nicotinic acetylcholine receptor in Alzheimer's disease. Neuroscience. 2002; 110(2):199–211.
36. Ong WY, Tanaka K, Dawe GS, Ittner LM, Farooqui AA. Slow excitotoxicity in Alzheimer's disease. J Alzheimers Dis. 2013; 35(4):643–668.
37. Schousboe A, Waagepetersen HS. Role of astrocytes in glutamate homeostasis: implications for excitotoxicity. Neurotox Res. 2005; 8(3-4):221–225.
38. Song MS, Baker GB, Dursun SM, Todd KG. The antidepressant phenelzine protects neurons and astrocytes against formaldehyde-induced toxicity. J Neurochem. 2010; 114(5):1405–1413.
39. Pereira C, Moreira P, Seiça R, Santos MS, Oliveira CR. Susceptibility to beta-amyloid-induced toxicity is decreased in goto-kakizaki diabetic rats: involvement of oxidative stress. Exp Neurol. 2000; 161(1):383–391.
40. Spillantini MG, Murrell JR, Goedert M, Farlow MR, Klug A, Ghetti B. Mutation in the tau gene in familial multiple system tauopathy with presenile dementia. Proc Natl Acad Sci U S A. 1998; 95(13):7737–7741.
41. Oddo S, Billings L, Kesslak JP, Cribbs DH, LaFerla FM. Abeta immunotherapy leads to clearance of early, but not late, hyperphosphorylated tau aggregates via the proteasome. Neuron. 2004; 43(3):321–332.
42. Busciglio J, Lorenzo A, Yeh J, Yankner BA. Beta-amyloid fibrils induce tau phosphorylation and loss of microtubule binding. Neuron. 1995; 14(4):879–888.
43. Götz J, Chen F, van Dorpe J, Nitsch RM. Formation of neurofibrillary tangles in P301l tau transgenic mice induced by Abeta 42 fibrils. Science. 2001; 293(5534):1491–1495.
44. Lewis J, Dickson DW, Lin WL, Chisholm L, Corral A, Jones G, et al. Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP. Science. 2001; 293(5534):1487–1491.
45. Alvarez G, Muñoz-Montaño JR, Satrústegui J, Avila J, Bogónez E, Díaz-Nido J. Regulation of tau phosphorylation and protection against beta-amyloid-induced neurodegeneration by lithium. Possible implications for Alzheimer's disease. Bipolar Disord. 2002; 4(3):153–165.
46. Ferrer I, Gomez-Isla T, Puig B, Freixes M, Ribé E, Dalfó E, et al. Current advances on different kinases involved in tau phosphorylation, and implications in Alzheimer's disease and tauopathies. Curr Alzheimer Res. 2005; 2(1):3–18.
47. Roberson ED, Scearce-Levie K, Palop JJ, Yan F, Cheng IH, Wu T, et al. Reducing endogenous tau ameliorates amyloid beta-induced deficits in an Alzheimer's disease mouse model. Science. 2007; 316(5825):750–754.
48. Ittner LM, Ke YD, Delerue F, Bi M, Gladbach A, van Eersel J, et al. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 2010; 142(3):387–397.
49. Rapoport M, Dawson HN, Binder LI, Vitek MP, Ferreira A. Tau is essential to beta -amyloid-induced neurotoxicity. Proc Natl Acad Sci U S A. 2002; 99(9):6364–6369.
50. El Khoury NB, Gratuze M, Papon MA, Bretteville A, Planel E. Insulin dysfunction and Tau pathology. Front Cell Neurosci. 2014; 8:22.
51. Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004; 27(5):1047–1053.
52. Craft S, Watson GS. Insulin and neurodegenerative disease: shared and specific mechanisms. Lancet Neurol. 2004; 3(3):169–178.
53. de la Monte SM, Wands JR. Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol. 2008; 2(6):1101–1113.
54. Sims-Robinson C, Kim B, Rosko A, Feldman EL. How does diabetes accelerate Alzheimer disease pathology? Nat Rev Neurol. 2010; 6(10):551–559.
55. Rönnemaa E, Zethelius B, Sundelöf J, Sundström J, Degerman-Gunnarsson M, Berne C, et al. Impaired insulin secretion increases the risk of Alzheimer disease. Neurology. 2008; 71(14):1065–1071.
56. Crane PK, Walker R, Hubbard RA, Li G, Nathan DM, Zheng H, et al. Glucose levels and risk of dementia. N Engl J Med. 2013; 369(6):540–548.
57. Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L. Diabetes mellitus and risk of dementia in the Kungsholmen project: a 6-year follow-up study. Neurology. 2004; 63(7):1181–1186.
58. S Roriz-Filho J, Sá-Roriz TM, Rosset I, Camozzato AL, Santos AC, Chaves ML, et al. (Pre)diabetes, brain aging, and cognition. Biochim Biophys Acta. 2009; 1792(5):432–443.
59. Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O'Brien PC, et al. Risk of dementia among persons with diabetes mellitus: a population-based cohort study. Am J Epidemiol. 1997; 145(4):301–308.
60. Ott A, Stolk RP, van Harskamp F, Pols HA, Hofman A, Breteler MM. Diabetes mellitus and the risk of dementia: the Rotterdam Study. Neurology. 1999; 53(9):1937–1942.
61. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA. Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol. 2004; 61(5):661–666.
62. Peila R, Rodriguez BL, Launer LJ. Honolulu-Asia Aging Study. Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies: the Honolulu-Asia Aging Study. Diabetes. 2002; 51(4):1256–1262.
63. Nelson TJ, Alkon DL. Insulin and cholesterol pathways in neuronal function, memory and neurodegeneration. Biochem Soc Trans. 2005; 33(Pt 5):1033–1036.
64. Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978; 272(5656):827–829.
65. Margolis RU, Altszuler N. Insulin in the cerebrospinal fluid. Nature. 1967; 215(5108):1375–1376.
66. Blázquez E, Velázquez E, Hurtado-Carneiro V, Ruiz-Albusac JM. Insulin in the brain: its pathophysiological implications for States related with central insulin resistance, type 2 diabetes and Alzheimer's disease. Front Endocrinol (Lausanne). 2014; 5(5108):5161.
67. Zhao W, Chen H, Xu H, Moore E, Meiri N, Quon MJ, et al. Brain insulin receptors and spatial memory. Correlated changes in gene expression, tyrosine phosphorylation, and signaling molecules in the hippocampus of water maze trained rats. J Biol Chem. 1999; 274(49):34893–34902.
68. Le Roith D, Zick Y. Recent advances in our understanding of insulin action and insulin resistance. Diabetes Care. 2001; 24(3):588–597.
69. Tremblay ML, Giguère V. Phosphatases at the heart of FoxO metabolic control. Cell Metab. 2008; 7(2):101–103.
70. Rankin CA, Sun Q, Gamblin TC. Tau phosphorylation by GSK-3beta promotes tangle-like filament morphology. Mol Neurodegener. 2007; 2(1):12.
71. Liu Y, Liu F, Grundke-Iqbal I, Iqbal K, Gong CX. Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. J Pathol. 2011; 225(1):54–62.
72. Phiel CJ, Wilson CA, Lee VM, Klein PS. GSK-3alpha regulates production of Alzheimer's disease amyloid-beta peptides. Nature. 2003; 423(6938):435–439.
73. Munoz L, Ammit AJ. Targeting p38 MAPK pathway for the treatment of Alzheimer's disease. Neuropharmacology. 2010; 58(3):561–568.
74. Otth C, Mendoza-Naranjo A, Mujica L, Zambrano A, Concha II, Maccioni RB. Modulation of the JNK and p38 pathways by cdk5 protein kinase in a transgenic mouse model of Alzheimer's disease. Neuroreport. 2003; 14(18):2403–2409.
75. Puig B, Gómez-Isla T, Ribé E, Cuadrado M, Torrejón-Escribano B, Dalfó E, et al. Expression of stress-activated kinases c-Jun N-terminal kinase (SAPK/JNK-P) and p38 kinase (p38-P), and tau hyperphosphorylation in neurites surrounding betaA plaques in APP Tg2576 mice. Neuropathol Appl Neurobiol. 2004; 30(5):491–502.
76. Quiroz-Baez R, Rojas E, Arias C. Oxidative stress promotes JNK-dependent amyloidogenic processing of normally expressed human APP by differential modification of alpha-, beta- and gamma-secretase expression. Neurochem Int. 2009; 55(7):662–670.
77. Zhao L, Teter B, Morihara T, Lim GP, Ambegaokar SS, Ubeda OJ, et al. Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: implications for Alzheimer's disease intervention. J Neurosci. 2004; 24(49):11120–11126.
78. Chesneau V, Vekrellis K, Rosner MR, Selkoe DJ. Purified recombinant insulin-degrading enzyme degrades amyloid beta-protein but does not promote its oligomerization. Biochem J. 2000; 351(Pt 2):509–516.
79. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, et al. Insulin-degrading enzyme regulates the levels of insulin, amyloid beta-protein, and the beta-amyloid precursor protein intracellular domain in vivo. Proc Natl Acad Sci U S A. 2003; 100(7):4162–4167.
80. Chan ES, Shetty MS, Sajikumar S, Chen C, Soong TW, Wong BS. ApoE4 expression accelerates hippocampus-dependent cognitive deficits by enhancing Aβ impairment of insulin signaling in an Alzheimer's disease mouse model. Sci Rep. 2016; 6(1):26119.
81. Starks EJ, Patrick O'Grady J, Hoscheidt SM, Racine AM, Carlsson CM, Zetterberg H, et al. Insulin resistance is associated with higher cerebrospinal fluid tau levels in asymptomatic APOEɛ4 carriers. J Alzheimers Dis. 2015; 46(2):525–533.
82. Hong M, Chen DC, Klein PS, Lee VM. Lithium reduces tau phosphorylation by inhibition of glycogen synthase kinase-3. J Biol Chem. 1997; 272(40):25326–25332.
83. Westwood AJ, Beiser A, Decarli C, Harris TB, Chen TC, He XM, et al. Insulin-like growth factor-1 and risk of Alzheimer dementia and brain atrophy. Neurology. 2014; 82(18):1613–1619.
84. Teppala S, Shankar A. Association between serum IGF-1 and diabetes among U.S. adults. Diabetes Care. 2010; 33(10):2257–2259.
85. Gregor MF, Hotamisligil GS. Inflammatory mechanisms in obesity. Annu Rev Immunol. 2011; 29(1):415–445.
86. Clark I, Atwood C, Bowen R, Paz-Filho G, Vissel B. Tumor necrosis factor-induced cerebral insulin resistance in Alzheimer's disease links numerous treatment rationales. Pharmacol Rev. 2012; 64(4):1004–1026.
87. Ferreira ST, Clarke JR, Bomfim TR, De Felice FG. Inflammation, defective insulin signaling, and neuronal dysfunction in Alzheimer's disease. Alzheimers Dement. 2014; 10(1):Suppl. S76–S83.
88. Perry VH, Nicoll JA, Holmes C. Microglia in neurodegenerative disease. Nat Rev Neurol. 2010; 6(4):193–201.
89. Swardfager W, Lanctôt K, Rothenburg L, Wong A, Cappell J, Herrmann N. A meta-analysis of cytokines in Alzheimer's disease. Biol Psychiatry. 2010; 68(10):930–941.
90. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-α- and obesity-induced insulin resistance. Science. 1996; 271(5249):665–668.
91. De Felice FG, Ferreira ST. Inflammation, defective insulin signaling, and mitochondrial dysfunction as common molecular denominators connecting type 2 diabetes to Alzheimer disease. Diabetes. 2014; 63(7):2262–2272.
92. Rains JL, Jain SK. Oxidative stress, insulin signaling, and diabetes. Free Radic Biol Med. 2011; 50(5):567–575.
93. Mahadev K, Zilbering A, Zhu L, Goldstein BJ. Insulin-stimulated hydrogen peroxide reversibly inhibits protein-tyrosine phosphatase 1b in vivo and enhances the early insulin action cascade. J Biol Chem. 2001; 276(24):21938–21942.
94. Meng TC, Fukada T, Tonks NK. Reversible oxidation and inactivation of protein tyrosine phosphatases in vivo. Mol Cell. 2002; 9(2):387–399.
95. Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, et al. Hyperinsulinemia provokes synchronous increases in central inflammation and β-amyloid in normal adults. Arch Neurol. 2005; 62(10):1539–1544.
96. Mrak RE, Griffin WS. Interleukin-1, neuroinflammation, and Alzheimer's disease. Neurobiol Aging. 2001; 22(6):903–908.
97. Plata-Salamán CR, ffrench-Mullen JM. Interleukin-1 beta inhibits Ca2+ channel currents in hippocampal neurons through protein kinase C. Eur J Pharmacol. 1994; 266(1):1–10.
98. Takeda S, Sato N, Uchio-Yamada K, Sawada K, Kunieda T, Takeuchi D, et al. Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc Natl Acad Sci U S A. 2010; 107(15):7036–7041.
99. Shah GN, Morofuji Y, Banks WA, Price TO. High glucose-induced mitochondrial respiration and reactive oxygen species in mouse cerebral pericytes is reversed by pharmacological inhibition of mitochondrial carbonic anhydrases: Implications for cerebral microvascular disease in diabetes. Biochem Biophys Res Commun. 2013; 440(2):354–358.
100. Erickson MA, Banks WA. Blood-brain barrier dysfunction as a cause and consequence of Alzheimer's disease. J Cereb Blood Flow Metab. 2013; 33(10):1500–1513.
101. Herz J, Strickland DK. LRP: a multifunctional scavenger and signaling receptor. J Clin Invest. 2001; 108(6):779–784.
102. Jaeger S, Pietrzik CU. Functional role of lipoprotein receptors in Alzheimer's disease. Curr Alzheimer Res. 2008; 5(1):15–25.
103. Deane R, Bell RD, Sagare A, Zlokovic BV. Clearance of amyloid-beta peptide across the blood-brain barrier: implication for therapies in Alzheimer's disease. CNS Neurol Disord Drug Targets. 2009; 8(1):16–30.
104. Yamada K, Hashimoto T, Yabuki C, Nagae Y, Tachikawa M, Strickland DK, et al. The low density lipoprotein receptor-related protein 1 mediates uptake of amyloid beta peptides in an in vitro model of the blood-brain barrier cells. J Biol Chem. 2008; 283(50):34554–34562.
105. Zlokovic BV, Deane R, Sagare AP, Bell RD, Winkler EA. Low-density lipoprotein receptor-related protein-1: a serial clearance homeostatic mechanism controlling Alzheimer's amyloid β-peptide elimination from the brain. J Neurochem. 2010; 115(5):1077–1089.
106. Liu LP, Hong H, Liao JM, Wang TS, Wu J, Chen SS, et al. Upregulation of RAGE at the blood-brain barrier in streptozotocin-induced diabetic mice. Synapse. 2009; 63(8):636–642.
107. Maragakis NJ, Rothstein JD. Mechanisms of Disease: astrocytes in neurodegenerative disease. Nat Clin Pract Neurol. 2006; 2(12):679–689.
108. Ahn KC, MacKenzie EM, Learman CR, Hall TC, Weaver CL, Dunbar GL, et al. Inhibition of p53 attenuates ischemic stress-induced activation of astrocytes. Neuroreport. 2015; 26(14):862–869.
109. Neal M, Richardson JR. Epigenetic regulation of astrocyte function in neuroinflammation and neurodegeneration. Biochim Biophys Acta Mol Basis Dis. 2018; 1864(2):432–443.
110. Eng LF, Ghirnikar RS, Lee YL. Glial fibrillary acidic protein: GFAP-thirty-one years (1969-2000). Neurochem Res. 2000; 25(9-10):1439–1451.
111. Song MS, Learman CR, Ahn KC, Baker GB, Kippe J, Field EM, et al. In vitro validation of effects of BDNF-expressing mesenchymal stem cells on neurodegeneration in primary cultured neurons of APP/PS1 mice. Neuroscience. 2015; 307:37–50.
112. Pekny M, Wilhelmsson U, Pekna M. The dual role of astrocyte activation and reactive gliosis. Neurosci Lett. 2014; 565:30–38.
113. Wang DD, Bordey A. The astrocyte odyssey. Prog Neurobiol. 2008; 86(4):342–367.
114. Heneka MT, Carson MJ, El Khoury J, Landreth GE, Brosseron F, Feinstein DL, et al. Neuroinflammation in Alzheimer's disease. Lancet Neurol. 2015; 14(4):388–405.
115. Newman EA. Glial cell regulation of neuronal activity and blood flow in the retina by release of gliotransmitters. Philos Trans R Soc Lond B Biol Sci. 2015; 370(1672):20140195.
116. Hawkins BT, Davis TP. The blood-brain barrier/neurovascular unit in health and disease. Pharmacol Rev. 2005; 57(2):173–185.
117. Abbott NJ. Blood-brain barrier structure and function and the challenges for CNS drug delivery. J Inherit Metab Dis. 2013; 36(3):437–449.
118. Ujiie M, Dickstein DL, Carlow DA, Jefferies WA. Blood-brain barrier permeability precedes senile plaque formation in an Alzheimer disease model. Microcirculation. 2003; 10(6):463–470.
119. Ma LY, Fei YL, Wang XY, Wu SD, Du JH, Zhu M, et al. The research on the relationship of RAGE, LRP-1, and Aβ Accumulation in the hippocampus, prefrontal lobe, and amygdala of STZ-induced diabetic rats. J Mol Neurosci. 2017; 62(1):1–10.
120. Herz J. Apolipoprotein E receptors in the nervous system. Curr Opin Lipidol. 2009; 20(3):190–196.
121. Abbott NJ, Rönnbäck L, Hansson E. Astrocyte-endothelial interactions at the blood-brain barrier. Nat Rev Neurosci. 2006; 7(1):41–53.
122. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, et al. Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment: a pilot clinical trial. Arch Neurol. 2012; 69(1):29–38.
123. McClean PL, Parthsarathy V, Faivre E, Hölscher C. The diabetes drug liraglutide prevents degenerative processes in a mouse model of Alzheimer's disease. J Neurosci. 2011; 31(17):6587–6594.
124. Cabou C, Burcelin R. GLP-1, the gut-brain, and brain-periphery axes. Rev Diabet Stud. 2011; 8(3):418–431.
125. During MJ, Cao L, Zuzga DS, Francis JS, Fitzsimons HL, Jiao X, et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med. 2003; 9(9):1173–1179.
126. McIntyre RS, Powell AM, Kaidanovich-Beilin O, Soczynska JK, Alsuwaidan M, Woldeyohannes HO, et al. The neuroprotective effects of GLP-1: possible treatments for cognitive deficits in individuals with mood disorders. Behav Brain Res. 2013; 237:164–171.
127. Li Y, Duffy KB, Ottinger MA, Ray B, Bailey JA, Holloway HW, et al. GLP-1 receptor stimulation reduces amyloid-beta peptide accumulation and cytotoxicity in cellular and animal models of Alzheimer's disease. J Alzheimers Dis. 2010; 19(4):1205–1219.
128. Gejl M, Gjedde A, Egefjord L, Møller A, Hansen SB, Vang K, et al. In Alzheimer's disease, 6-month treatment with GLP-1 analog prevents decline of brain glucose metabolism: randomized, placebo-controlled, double-blind clinical trial. Front Aging Neurosci. 2016; 8(8):108.
129. Gejl M, Brock B, Egefjord L, Vang K, Rungby J, Gjedde A. Blood-brain glucose transfer in Alzheimer's disease: effect of GLP-1 analog treatment. Sci Rep. 2017; 7(1):17490.
130. Li J, Deng J, Sheng W, Zuo Z. Metformin attenuates Alzheimer's disease-like neuropathology in obese, leptin-resistant mice. Pharmacol Biochem Behav. 2012; 101(4):564–574.
131. Hsu CC, Wahlqvist ML, Lee MS, Tsai HN. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin. J Alzheimers Dis. 2011; 24(3):485–493.
132. Imfeld P, Bodmer M, Jick SS, Meier CR. Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study. J Am Geriatr Soc. 2012; 60(5):916–921.
133. Moore EM, Mander AG, Ames D, Kotowicz MA, Carne RP, Brodaty H, et al. Increased risk of cognitive impairment in patients with diabetes is associated with metformin. Diabetes Care. 2013; 36(10):2981–2987.
134. Cohen P, Goedert M. GSK3 inhibitors: development and therapeutic potential. Nat Rev Drug Discov. 2004; 3(6):479–487.
135. Eldar-Finkelman H, Krebs EG. Phosphorylation of insulin receptor substrate 1 by glycogen synthase kinase 3 impairs insulin action. Proc Natl Acad Sci U S A. 1997; 94(18):9660–9664.
136. Stambolic V, Ruel L, Woodgett JR. Lithium inhibits glycogen synthase kinase-3 activity and mimics wingless signalling in intact cells. Curr Biol. 1996; 6(12):1664–1668.
137. Muñoz-Montaño JR, Moreno FJ, Avila J, Diaz-Nido J. Lithium inhibits Alzheimer's disease-like tau protein phosphorylation in neurons. FEBS Lett. 1997; 411(2-3):183–188.
138. Landreth G, Jiang Q, Mandrekar S, Heneka M. PPARgamma agonists as therapeutics for the treatment of Alzheimer's disease. Neurotherapeutics. 2008; 5(3):481–489.
139. Bookout AL, Jeong Y, Downes M, Yu RT, Evans RM, Mangelsdorf DJ. Anatomical profiling of nuclear receptor expression reveals a hierarchical transcriptional network. Cell. 2006; 126(4):789–799.
140. Yan Q, Zhang J, Liu H, Babu-Khan S, Vassar R, Biere AL, et al. Anti-inflammatory drug therapy alters beta-amyloid processing and deposition in an animal model of Alzheimer's disease. J Neurosci. 2003; 23(20):7504–7509.
141. Pedersen WA, Flynn ER. Insulin resistance contributes to aberrant stress responses in the Tg2576 mouse model of Alzheimer's disease. Neurobiol Dis. 2004; 17(3):500–506.
142. Ceconi C, Francolini G, Bastianon D, Gitti GL, Comini L, Ferrari R. Differences in the effect of angiotensin-converting enzyme inhibitors on the rate of endothelial cell apoptosis: in vitro and in vivo studies. Cardiovasc Drugs Ther. 2007; 21(6):423–429.
143. Umegaki H. Therapeutic potential of antidiabetic medications in the treatment of cognitive dysfunction and dementia. Drugs Aging. 2016; 33(6):399–409.