Glucose tolerance and insulin sensitivity are impaired in APP/PS1 transgenic mice prior to amyloid plaque pathogenesis and cognitive decline

Experimental Gerontology

Volumn 88, Issue , 2017, Pages 9-18

  Macklin, Lauren ^a,b   Griffith, Chelsea M ^a,b   Cai, Yan ^a,b,c   Rose, Gregory M ^a,b   Yan, Xiao Xin ^a,b,c   Patrylo, Peter R ^a,b  

^a SOUTHERN ILLINOIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SOUTHERN ILLINOIS UNIVERSITY   (United States)

^c Central South University   (China)

Author keywords

Alzheimer's disease; Hippocampus; Morris water maze; Pre diabetic

Indexed keywords

AMYLOID BETA PROTEIN[1-42]; AMYLOID PRECURSOR PROTEIN; GLUCOSE; INSULIN; GLUCOSE BLOOD LEVEL; PRESENILIN 1; PRESENILIN 1, MOUSE;

AGE; ALZHEIMER DISEASE; AMYLOID PLAQUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; APP PS1 TRANSGENIC MOUSE; ARTICLE; C57BL 6 MOUSE; COGNITIVE DEFECT; CONTROLLED STUDY; DISEASE COURSE; GLUCOSE BLOOD LEVEL; GLUCOSE TOLERANCE; GLUCOSE TOLERANCE TEST; HUMAN; IMMUNOREACTIVITY; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; INTRAPERITONEAL GLUCOSE TOLERANCE TEST; MALE; MEMORY DISORDER; METABOLIC DISORDER; MOUSE; NEUROPATHOLOGY; NONHUMAN; PATHOGENESIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN EXPRESSION; TRANSGENIC MOUSE; TREND STUDY; WILD TYPE; ANALYSIS; ANIMAL; BLOOD; C57BL MOUSE; COMPLICATION; DISEASE MODEL; GENETICS; HIPPOCAMPUS; INSULIN RESISTANCE; PATHOLOGY;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; BLOOD GLUCOSE; COGNITIVE DYSFUNCTION; DISEASE MODELS, ANIMAL; GLUCOSE TOLERANCE TEST; HIPPOCAMPUS; HUMANS; INSULIN; INSULIN RESISTANCE; MALE; MICE; MICE, INBRED C57BL; MICE, TRANSGENIC; PLAQUE, AMYLOID; PRESENILIN-1;

EID: 85008323058     PISSN: 05315565     EISSN: 18736815     Source Type: Journal    
DOI: 10.1016/j.exger.2016.12.019     Document Type: Article

References (104)

1. Attems, J., Jellinger, K.A., The overlap between vascular disease and Alzheimer's disease—lessons from pathology. BMC Med., 12, 2014, 206.
2. Bailey, C.J., Matty, A.J., Glucose tolerance and plasma insulin of the rat in relation to the oestrous cycle and sex hormones. Horm. Metab. Res. 4 (1972), 266–270.
3. Banks, W.A., Owen, J.B., Erickson, M.A., Insulin in the brain: there and back again. Pharmacol. Ther. 136 (2012), 82–93.
4. Bedse, G., Di Domenico, F., Serviddio, G., Cassano, T., Aberrant insulin signaling in Alzheimer's disease: current knowledge. Front. Neurosci., 9, 2015, 204.
5. Beeri, M.S., Schmeidler, J., Silverman, J.M., Gandy, S., Wysocki, M., Hannigan, C.M., Purohit, D.P., Lesser, G., Grossman, H.T., Haroutunian, V., Insulin in combination with other diabetes medication is associated with less Alzheimer neuropathology. Neurology 71 (2008), 750–757.
6. Bendheim, P.E., Brown, H.R., Rudelli, R.D., Scala, L.J., Goller, N.L., Wen, G.Y., Kascsak, R.J., Cashman, N.R., Bolton, D.C., Nearly ubiquitous tissue distribution of the scrapie agent precursor protein. Neurology, 42, 1992, 149.
7. Bickeböller, H., Campion, D., Brice, A., Amouyel, P., Hannequin, D., Didierjean, O., Penet, C., Martin, C., Pérez-Tur, J., Michon, A., Dubois, B., Ledoze, F., Thomas-Anterion, C., Pasquier, F., Puel, M., Demonet, J.F., Moreaud, O., Babron, M.C., Meulien, D., Guez, D., Chartier-Harlin, M.C., Frebourg, T., Agid, Y., Martinez, M., Clerget-Darpoux, F., Apolipoprotein E and Alzheimer disease: genotype-specific risks by age and sex. Am. J. Hum. Genet. 60 (1997), 439–446.
8. Biessels, G.J., Deary, I.J., Ryan, C.M., Cognition and diabetes: a lifespan perspective. Lancet Neurol. 7 (2008), 184–190.
9. Cai, Y., Xiong, K., Zhang, X.M., Cai, H., Luo, X.G., Feng, J.C., Clough, R.W., Struble, R.G., Patrylo, P.R., Chu, Y., Kordower, J.H., Yan, X.X., β-Secretase-1 elevation in aged monkey and Alzheimer's disease human cerebral cortex occurs around the vasculature in partnership with multisystem axon terminal pathogenesis and β-amyloid accumulation. Eur. J. Neurosci. 32 (2010), 1223–1238.
10. Cao, D., Lu, H., Lewis, T.L., Li, L., Intake of sucrose-sweetened water induces insulin resistance and exacerbates memory deficits and amyloidosis in a transgenic mouse model of Alzheimer disease. J. Biol. Chem. 282 (2007), 36275–36282.
11. Chen, Y., Liang, Z., Tian, Z., Blanchard, J., Dai, C.-L., Chalbot, S., Gong, C.-X., Intracerebroventricular streptozotocin exacerbates Alzheimer-like changes of 3xTg-AD mice. Mol. Neurobiol. 49 (2013), 547–562.
12. Chen, Y., Zhang, J., Zhang, B., Gong, C.X., Targeting insulin signaling for the treatment of Alzheimer's disease. Curr. Top. Med. Chem. 16 (2016), 485–492.
13. Claxton, A., Baker, L.D., Hanson, A., Trittschuh, E.H., Cholerton, B., Morgan, A., Callaghan, M., Arbuckle, M., Behl, C., Craft, S., Long acting intranasal insulin improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia. J. Alzheimers Dis. 45 (2015), 1269–1270.
14. Clee, S.M., Attie, A.D., The genetic landscape of type 2 diabetes in mice. Endocr. Rev. 28.1 (2007), 48–83 (2007).
15. 125I-insulin binding sites in the rat hypothalamus by quantitative autoradiography. Neurosci. Lett. 70 (1986), 17–22.
16. Coyle, J.T., Price, D.L., DeLong, M.R., Alzheimer's disease: a disorder of cortical cholinergic innervation. Science 219 (1983), 1184–1190.
17. Deng, X., Li, M., Ai, W., He, L., Lu, D., Patrylo, P.R., Cai, H., Luo, X., Li, Z., Yan, X., Lipolysaccharide-induced neuroinflammation is associated with Alzheimer-like amyloidogenic axonal pathology and dendritic degeneration in rats. Adv. Alzheimer Dis. 3 (2014), 78–93.
18. Du, L.L., Xie, J.Z., Cheng, X.S., Li, X.H., Kong, F.L., Jiang, X., Ma, Z.W., Wang, J.Z., Chen, C., Zhou, X.W., Activation of sirtuin 1 attenuates cerebral ventricular streptozotocin-induced tau hyperphosphorylation and cognitive injuries in rat hippocampi. Age (Dordr.) 36 (2014), 613–623.
19. Duffy, A.M., Hölscher, C., The incretin analogue D-Ala 2 GIP reduces plaque load, astrogliosis and oxidative stress in an APP/PS1 mouse model of Alzheimer's disease. Neurosci. 228 (2013), 294–300.
20. Escribano, L., Simón, A.M., Gimeno, E., Cuadrado-Tejedor, M., de Maturana, R.L., García-Osta, A., Frechilla, D., Rosiglitazone rescues memory impairment in Alzheimer's transgenic mice: mechanisms involving a reduced amyloid and tau pathology. Neuropsychopharmacology 35 (2010), 1593–1604.
21. Feart, C., Samieri, C., Barberger-Gateau, P., Mediterranean diet and cognitive health: an update of available knowledge. Curr. Opin. Clin. Nutr. Metab. Care 18 (2015), 51–62.
22. Fontaine, D.A., Davis, D.B., Attention to background strain is essential for metabolic research: C57BL/6 and the International Knockout Mouse Consortium. Diabetes 65 (2016), 25–33.
23. Giménez-Llort, L., García, Y., Buccieri, K., Revilla, S., Sunol, C., Cristofol, R., Sanfeliu, C., Gender-specific neuroimmunoendocrine response to treadmill exercise in 3xTg-AD mice. Int. J. Alzheimers Dis., 2010.
24. González-Domínguez, R., García-Barrera, T., Vitorica, J., Gómez-Ariza, J.L., Metabolomic screening of regional brain alterations in the APP/PS1 transgenic model of Alzheimer's disease by direct infusion mass spectrometry. J. Pharm. Biomed. Anal. 102 (2015), 425–435.
25. Guo, Q., Fu, W., Sopher, B.L., Miller, M.W., Ware, C.B., Martin, G.M., Mattson, M.P., Increased vulnerability of hippocampal neurons to excitotoxic necrosis in presenilin-1 mutant knock-in mice. Nat. Med. 5 (1999), 101–106.
26. Havrankova, J., Roth, J., Brownstein, M., Insulin receptors are widely distributed in the central nervous system of the rat. Nature 272 (1978), 827–829.
27. Hayashi-Park, E., Ozment, B.N., Griffith, C.M., Zhang, H., Patrylo, P.R., Rose, G.M., Experimentally induced diabetes worsens neuropathology, but not learning and memory, in middle aged 3xTg mice. Behav. Brain Res., 2016 (Epub ahead of print).
28. Heneka, M.T., Carson, M.J., El Khoury, J., Landreth, G.E., Brosseron, F., Feinstein, D.L., Jacobs, A.H., Wyss-Coray, T., Vitorica, J., Ransohoff, R.M., Herrup, K., Frautschy, S.A., Finsen, B., Brown, G.C., Verkhratsky, A., Yamanaka, K., Koistinaho, J., Latz, E., Halle, A., Petzold, G.C., Town, T., Morgan, D., Shinohara, M.L., Perry, V.H., Holmes, C., Bazan, N.G., Brooks, D.J., Hunot, S., Joseph, B., Deigendesch, N., Garaschuk, O., Boddeke, E., Dinarello, C.A., Breitner, J.C., Cole, G.M., Golenbock, D.T., Kummer, M.P., Neuroinflammation in Alzheimer's disease. Lancet Neurol. 14 (2015), 388–405.
29. Heo, J.H., Lee, S.R., Lee, S.T., Lee, K.M., Oh, J.H., Jang, D.P., Chang, K.T., Cho, Z.H., Spatial distribution of glucose hypometabolism induced by intracerebroventricular streptozotocin in monkeys. J. Alzheimers Dis. 25 (2011), 517–523.
30. Heppner, F.L., Ransohoff, R.M., Becher, B., Immune attack: the role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 16 (2015), 358–372.
31. Hettich, M.M., Matthes, F., Ryan, D.P., Griesche, N., Schröder, S., Dorn, S., Krauβ, S., Ehninger, D., The anti-diabetic drug metformin reduces BACE1 protein level by interfering with the MID1 complex. PLoS, 2014, e102420.
32. Hölscher, C., Lin, L., New roles for insulin-like hormones in neuronal signalling and protection: New hopes for novel treatments of Alzheimer's disease. Neurobiol. Aging 31 (2010), 1495–1502.
33. Hotamisligil, G.K.S., Peraldi, P., Budavari, A., Ellis, R., White, M.F., Spiegelman, B.M., IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271 (1996), 665–670, 10.1126/science.271.5249.665.
34. Jack, C.R. Jr., Wiste, H.J., Weigand, S.D., Knopman, D.S., Vemuri, P., Mielke, M.M., Lowe, V., Senjem, M.L., Gunter, J.L., Machulda, M.M., Gregg, B.E., Pankratz, V.S., Rocca, W.A., Petersen, R.C., Age, sex, and APOE ε4 effects on memory, brain structure, and β-amyloid across the adult life span. JAMA Neurol. 72 (2015), 511–519.
35. Jankowsky, J.L., Slunt, H.H., Ratovitski, T., Jenkins, N.A., Copeland, N.G., Borchelt, D.R., Co-expression of multiple transgenes in mouse CNS: a comparison of strategies. Biomol. Eng. 17 (2001), 157–165.
36. Jankowsky, J.L., Fadale, D.J., Anderson, J., Xu, G.M., Gonzales, V., Jenkins, N.A., Copeland, N.G., Lee, M.K., Younkin, L.H., Wagner, S.L., Younkin, S.G., Borchelt, D.R., Mutant presenilins specifically elevate the levels of the 42 residue beta-amyloid peptide in vivo: evidence for augmentation of a 42-specific gamma secretase. Hum. Mol. Genet. 13 (2004), 159–170.
37. Joost, H.G., Schürmann, A., The genetic basis of obesity-associated type 2 diabetes (diabesity) in polygenic mouse models. Mamm. Genome 25 (2014), 401–412.
38. Kamal, A., Biessels, G.J., Ramakers, G.M., Gispen, W.H., The effect of short duration streptozotocin-induced diabetes mellitus on the late phase and threshold of long-term potentiation induction in the rat. Brain Res. 1053 (2005), 126–130.
39. Knight, E.M., Martins, I.V., Gümüsgöz, S., Allan, S.M., Lawrence, C.B., High-fat diet-induced memory impairment in triple-transgenic Alzheimer's disease (3xTgAD) mice is independent of changes in amyloid and tau pathology. Neurobiol. Aging 35 (2014), 1821–1832.
40. Knight, E.M., Ruiz, H.H., Kim, S.H., Harte, J.C., Hsieh, W., Glabe, C., Klein, W.L., Attie, A.D., Buettner, C., Ehrlich, M.E., Gandy, S., Unexpected partial correction of metabolic and behavioral phenotypes of Alzheimer's APP/PSEN1 mice by gene targeting of diabetes/Alzheimer's-related Sorcs1. Acta Neuropathol. Commun., 4, 2016, 1.
41. Kurt, M.A., Davies, D.C., Kidd, M., Duff, K., Rolph, S.C., Jennings, K.H., Howlett, D.R., Neurodegenerative changes associated with beta-amyloid deposition in the brains of mice carrying mutant amyloid precursor protein and mutant presenilin-1 transgenes. Exp. Neurol. 171 (2001), 59–71.
42. Lagathu, C., Bastard, J.-P., Auclair, M., Maachi, M., Capeau, J., Caron, M., Chronic interleukin-6 (IL-6) treatment increased IL-6 secretion and induced insulin resistance in adipocyte: prevention by rosiglitazone. Biochem. Biophys. Res. Commun. 311 (2003), 372–379.
43. Lambert, J.C., Berr, C., Pasquier, F., Delacourte, A., Frigard, B., Cottel, D., Pérez-Tur, J., Mouroux, V., Mohr, M., Cécyre, D., Galasko, D., Pronounced impact of Th1/E47cs mutation compared with − 491 AT mutation on neural APOE gene expression and risk of developing Alzheimer's disease. Hum. Mol. Genet. 7 (1998), 1511–1516.
44. Lane-Donovan, C., Philips, G.T., Herz, J., More than cholesterol transporters: lipoprotein receptors in CNS function and neurodegeneration. Neuron 83 (2014), 771–787.
45. Lannert, H., Hoyer, S., Intracerebroventricular administration of streptozotocin causes long-term diminutions in learning and memory abilities and in cerebral energy metabolism in adult rats. Behav. Neurosci. 112 (1998), 1199–1208.
46. Leibson, C.L., Rocca, W.A., Hanson, V.A., Cha, R., Kokmen, E., O'Brien, P.C., Palumbo, P.J., The risk of dementia among persons with diabetes mellitus: a population-based cohort study. Ann. N. Y. Acad. Sci. 826 (1997), 422–427.
47. Lenard, N.R., Berthoud, H.-R., Central and peripheral regulation of food intake and physical activity: pathways and genes. Obesity 16 (2008), 11–22.
48. Lester-Coll, N., Rivera, E.J., Soscia, S.J., Doiron, K., Wands, J.R., de la Monte, S.M., Intracerebral streptozotocin model of type 3 diabetes: relevance to sporadic Alzheimer's disease. J.Alzheimers Dis. 9 (2006), 13–33.
49. Li, J.M., Cai, Y., Liu, F., Yang, L., Hu, X., Patrylo, P.R., Cai, H., Luo, X.G., Xiao, D., Yan, X.X., Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum. Oncotarget 6 (2015), 10772–10785.
50. Ma, L., Shao, Z., Wang, R., Zhao, Z., Dong, W., Zhang, J., Zhang, X., Sheng, S., Ji, Z., Zhang, J., Rosiglitazone improves learning and memory ability in rats with type 2 diabetes through the insulin signaling pathway. Am. J. Med. Sci. 350 (2015), 121–128.
51. Mayer, G., Nitsch, R., Hoyer, S., Effects of changes in peripheral and cerebral glucose metabolism on locomotor activity, learning and memory in adult male rats. Brain Res. 532 (1990), 95–100.
52. McClean, P.L., Hölscher, C., Liraglutide can reverse memory impairment, synaptic loss and reduce plaque load in aged APP/PS1 mice, a model of Alzheimer's disease. Neuropharm. 76 (2014), 57–67.
53. McNay, E.C., Ong, C.T., McCrimmon, R.J., Cresswell, J., Bogan, J.S., Sherwin, R.S., Hippocampal memory processes are modulated by insulin and high-fat-induced insulin resistance. Neurobiol. Learn. Mem. 93 (2010), 546–553.
54. Mehla, J., Chauhan, B.C., Chauhan, N.B., 2014. Experimental induction of type 2 diabetes in aging-accelerated mice triggered Alzheimer-like pathology and memory deficits. J. Alzheimers Dis. 39, 145–162.
55. Meneilly, G.S., Hill, A., Alterations in glucose metabolism in patients with Alzheimer's disease. J. Am. Geriatr. Soc. 41 (1993), 710–714.
56. Michaelson, D.M., APOE ε4: the most prevalent yet understudied risk factor for Alzheimer's disease. Alzheimers Dement. 10 (2014), 861–868.
57. Mody, N., Agouni, A., McIlroy, G.D., Platt, B., Delibegovic, M., Susceptibility to diet-induced obesity and glucose intolerance in the APP SWE/PSEN1 A246E mouse model of Alzheimer's disease is associated with increased brain levels of protein tyrosine phosphatase 1B (PTP1B) and retinol-binding protein 4 (RBP4), and basal phosphorylation of S6 ribosomal protein. Diabetologia 54 (2011), 2143–2151.
58. Moloney, A.M., Griffin, R.J., Timmons, S., O'Connor, R., Ravid, R., O'Neill, C., Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signaling. Neurobiol. Aging 31 (2010), 224–243.
59. Monsell, S.E., Kukull, W.A., Roher, A.E., Maarouf, C.L., Serrano, G., Beach, T.G., Caselli, R.J., Montine, T.J., Reiman, E.M., Characterizing apolipoprotein E ε4 carriers and noncarriers with the clinical diagnosis of mild to moderate Alzheimer dementia and minimal β-amyloid peptide plaques. JAMA Neurol., 2015, 10.1001/jamaneurol.2015.1721.
60. Morgen, K., Frölich, L., The metabolism hypothesis of Alzheimer's disease: from the concept of central insulin resistance and associated consequences to insulin therapy. J. Neural Transm. 122 (2015), 499–504.
61. Mosconi, L., Pupi, A., De Leon, M.J., Brain glucose hypometabolism and oxidative stress in preclinical Alzheimer's disease. Ann. N. Y. Acad. Sci. 1147 (2008), 180–195.
62. Mushtaq, G., Greig, N.H., Khan, J.A., Kamal, M.A., Status of acetylcholinesterase and butyrylcholinesterase in Alzheimer's disease and type 2 diabetes mellitus. CNS Neurol. Disord. Drug Targets 13 (2014), 1432–1439.
63. O'Leary, T.P., Brown, R.E., Visuo-spatial learning and memory deficits on the Barnes maze in the 16-month-old APPswe/PS1dE9 mouse model of Alzheimer's disease. Behav. Brain Res. 201 (2009), 120–127.
64. O'Reilly, J.A., Lynch, M., Rosiglitazone improves spatial memory and decreases insoluble Aβ1–42 in APP/PS1 mice. J. NeuroImmune Pharmacol. 7 (2012), 140–144.
65. Ogomori, K., Kitamoto, T., Tateishi, J., Sato, Y., Suetsugu, M., Abe, M., Beta-protein amyloid is widely distributed in the central nervous system of patients with Alzheimer's disease. Am. J. Pathol., 134, 1989, 243.
66. Orr, M.E., Salinas, A., Buffenstein, R., Oddo, S., Mammalian target of rapamycin hyperactivity mediates the detrimental effects of a high sucrose diet on Alzheimer's disease pathology. Neurobiol. Aging 35 (2014), 1233–1242.
67. Ott, A., Stolk, R.P., Hofman, A., van Harskamp, F., Grobbee, D.E., Breteler, M.M., Association of diabetes mellitus and dementia: the Rotterdam Study. Diabetologia 39 (1996), 1392–1397.
68. Pedrós, I., Petrov, D., Allgaier, M., Sureda, F., Barroso, E., Beas-Zarate, C., Auladell, C., Pallàs, M., Vázquez-Carrera, M., Casadesús, G., Folch, J., Early alterations in energy metabolism in the hippocampus of APPswe/PS1dE9 mouse model of Alzheimer's disease. BBA MOL BAS 1842 (2014), 1556–1566.
69. Praticò, D., Evidence of oxidative stress in Alzheimer's disease brain and antioxidant therapy: lights and shadows. Ann. N. Y. Acad. Sci. 1147 (2008), 70–78.
70. Razay, G., Vreugdenhil, A., Wilcock, G., The metabolic syndrome and Alzheimer disease. Arch. Neurol. 64 (2007), 93–96.
71. Rogaev, E.I., Sherrington, R., Rogaeva, E.A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., et al. Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376 (1995), 775–778.
72. Rönnemaa, E., Zethelius, B., Sundelöf, J., Sundström, J., Degerman-Gunnarsson, M., Berne, C., Lannfelt, L., Kilander, L., Impaired insulin secretion increases the risk of Alzheimer disease. Neurology 71 (2008), 1065–1071.
73. Rotter, V., Nagaev, I., Smith, U., Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-, overexpressed in human fat cells from insulin-resistant subjects. J. Biol. Chem. 278 (2003), 45777–45784.
74. Rui, L., Aguirre, V., Kim, J.K., Shulman, G.I., Lee, A., Corbould, A.,.. White, M.F., Insulin/IGF-1 and TNF-alpha stimulate phosphorylation of IRS-1 at inhibitory Ser307 via distinct pathways. JCI 107 (2001), 181–189.
75. Sadowski, M., Pankiewicz, J., Scholtzova, H., Ji, Y., Quartermain, D., Jensen, C.H., Duff, K., Nixon, R.A., Gruen, R.J., Wisniewski, T., Amyloid-β deposition is associated with decreased hippocampal glucose metabolism and spatial memory impairment in APP/PS1 mice. J. Neuropathol. Exp. Neurol. 63 (2004), 418–428.
76. Salkovic-Petrisic, M., Knezovic, A., Hoyer, S., Riederer, P., What have we learned from the streptozotocin-induced animal model of sporadic Alzheimer's disease, about the therapeutic strategies in Alzheimer's research. J. Neural Transm. 120 (2013), 233–252.
77. Scheibel, A.B., Duong, T.H., Jacobs, R., Alzheimer's disease as a capillary dementia. Ann. Med. 21 (1989), 103–107.
78. Schulingkamp, R.J., Pagano, T.C., Hung, D., Raffa, R.B., Insulin receptors and insulin action in the brain: review and clinical implications. Neurosci. Biobehav. Rev. 24 (2000), 855–872.
79. Searcy, J.L., Phelps, J.T., Pancani, T., Kadish, I., Popovic, J., Anderson, K.L., Beckett, T.L., Murphy, M.P., Chen, K.C., Blalock, E.M., Landfield, P.W., Long-term pioglitazone treatment improves learning and attenuates pathological markers in a mouse model of Alzheimer's disease. J. Alzheimers Dis. 30 (2012), 943–961.
80. Sherrington, R., Rogaev, E.I., Liang, Y., Rogaeva, E.A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J.F., Bruni, A.C., Montesi, M.P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., Chumakov, I., Pollen, D., Brookes, A., Sanseau, P., Polinsky, R.J., Wasco, W., Da Silva, H.A., Haines, J.L., Perkicak-Vance, M.A., Tanzi, R.E., Roses, A.D., Fraser, P.E., Rommens, J.M., St George-Hyslop, P.H., Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375 (1995), 754–760.
81. Snyder, H.M., Corriveau, R.A., Craft, S., Faber, J.E., Greenberg, S.M., Knopman, D., Lamb, B.T., Montine, T.J., Nedergaard, M., Schaffer, C.B., Schneider, J.A., Wellington, C., Wilcock, D.M., Zipfel, G.J., Zlokovic, B., Bain, L.J., Bosetti, F., Galis, Z.S., Koroshetz, W., Carrillo, M.C., Vascular contributions to cognitive impairment and dementia including Alzheimer's disease. Alzheimers Dement. 11 (2015), 710–717.
82. Sonnen, J.A., Larson, E.B., Brickell, K., Crane, P.K., Woltjer, R., Montine, T.J., Craft, S., Different patterns of cerebral injury in dementia with or without diabetes. Arch. Neurol. 66 (2009), 315–322.
83. Standaert, D.G., Lee, V.M., Greenberg, B.D., Lowery, D.E., Trojanowski, J.Q., Molecular features of hypothalamic plaques in Alzheimer's disease. Am. J. Pathol., 139, 1991, 681.
84. Steen, E., Terry, B.M., Rivera, E.J., Cannon, J.L., Neely, T.R., Tavares, R., Xu, X.J., Wands, J.R., de la Monte, S.M., Impaired insulin and insulin-like growth factor expression and signaling mechanisms in Alzheimer's disease–is this type 3 diabetes?. J. Alzheimers Dis. 7 (2005), 63–80.
85. Stern, Y., Brandt, J., Albert, M., Jacobs, D.M., Liu, X., Bell, K., Marder, K., Sano, M., Albert, S., Del-Castillo Castenada, C., Bylsma, F., Tycko, B., Mayeux, R., The absence of an apolipoprotein epsilon4 allele is associated with a more aggressive form of Alzheimer's disease. Ann. Neurol. 41 (1997), 615–620.
86. Struble, R.G., Ala, T., Patrylo, P.R., Brewer, G.J., Yan, X.X., Is brain amyloid production a cause or a result of dementia of the Alzheimer's type?. J. Alzheimers Dis. 22 (2010), 393–399.
87. Takeda, S., Sato, N., Uchio-Yamada, K., Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., Morishita, R., Elevation of plasma β-amyloid level by glucose loading in Alzheimer mouse models. Biochem. Biophys. Res. Commun. 385 (2009), 93–197.
88. Takeda, S., Sato, N., Uchio-Yamada, K., Sawada, K., Kunieda, T., Takeuchi, D., Kurinami, H., Shinohara, M., Rakugi, H., Morishita, R., Diabetes-accelerated memory dysfunction via cerebrovascular inflammation and Aβ deposition in an Alzheimer mouse model with diabetes. PNAS 107 (2010), 7036–7041.
89. Talbot, K., Wang, H.Y., Kazi, H., Han, L.Y., Bakshi, K.P., Stucky, A., Fuino, R.L., Kawaguchi, K.R., Samoyedny, A.J., Wilson, R.S., Arvanitakis, Z., Demonstrated brain insulin resistance in Alzheimer's disease patients is associated with IGF-1 resistance, IRS-1 dysregulation, and cognitive decline. JCI 122 (2012), 1316–1338.
90. Tanahashi, H., Mitsunaga, Y., Takahashi, K., Tasaki, H., Watanabe, S., Tabira, T., Missense mutation of S182 gene in Japanese familial Alzheimer's disease. Lancet, 346, 1995, 440.
91. Thinakaran, G., Regard, J.B., Bouton, C.M., Harris, C.L., Price, D.L., Borchelt, D.R., Sisodia, S.S., Stable association of presenilin derivatives and absence of presenilin interactions with APP. Neurobiol. Dis. 4 (1998), 438–453.
92. Trinchese, F., Liu, S., Battaglia, F., Walter, S., Mathews, P.M., Arancio, O., Progressive age-related development of Alzheimer-like pathology in APP/PS1 mice. Ann. Neurol. 55 (2004), 801–814.
93. Valente, T., Gella, A., Fernàndez-Busquets, X., Unzeta, M., Durany, N., Immunohistochemical analysis of human brain suggests pathological synergism of Alzheimer's disease and diabetes mellitus. Neurobiol. Dis. 37 (2010), 67–76.
94. Vandal, M., White, P.J., Chevrier, G., Tremblay, C., St-Amour, I., Planel, E., Marette, A., Calon, F., Age-dependent impairment of glucose tolerance in the 3xTg-AD mouse model of Alzheimer's disease. FASEB J., 2015 (pii: fj.14-268482).
95. Volianskis, A., Køstner, R., Mølgaard, M., Hass, S., Jensen, M.S., Episodic memory deficits are not related to altered glutamatergic synaptic transmission and plasticity in the CA1 hippocampus of the APPswe/PS1δE9-deleted transgenic mice model of β-amyloidosis. Neurobiol. Aging 31 (2010), 1173–1187.
96. Wang, J., Tanila, H., Puoliväli, J., Kadish, I., van Groen, T., Gender differences in the amount and deposition of amyloidbeta in APPswe and PS1 double transgenic mice. Neurobiol. Dis. 14 (2003), 318–327.
97. Willette, A.A., Bendlin, B.B., Starks, E.J., Birdsill, A.C., Johnson, S.C., Christian, B.T., Okonkwo, O.C., La Rue, A., Hermann, B.P., Koscik, R.L., Jonaitis, E.M., Sager, M.A., Asthana, S., Association of insulin resistance with cerebral glucose uptake in late middle-aged adults at risk for Alzheimer disease. JAMA Neurol., 2015, 10.1001/jamaneurol.2015.0613.
98. Wirths, O., Breyhan, H., Marcello, A., Cotel, M.C., Brück, W., Bayer, T.A., Inflammatory changes are tightly associated with neurodegeneration in the brain and spinal cord of the APP/PS1KI mouse model of Alzheimer's disease. Neurobiol. Aging 31 (2010), 747–757.
99. Xue, Z.Q., He, Z.W., Yu, J.J., Cai, Y., Qiu, W.Y., Pan, A., Gai, W.P., Cai, H., Luo, X.G., Ma, C., Yan, X.X., Non-neuronal and neuronal BACE1 elevation in association with angiopathic and leptomeningeal β-amyloid deposition in the human brain. BMC Neurol., 15, 2015, 71.
100. Yang, Y., Zhang, J., Ma, D., Zhang, M., Hu, S., Shao, S., Gong, C.X., Subcutaneous administration of liraglutide ameliorates Alzheimer-associated tau hyperphosphorylation in rats with type 2 diabetes. J. Alzheimers Dis. 37 (2013), 637–648.
101. Yannakoulia, M., Kontogianni, M., Scarmeas, N., Cognitive health and Mediterranean diet: just diet or lifestyle pattern?. Ageing Res. Rev. 20 (2015), 74–78.
102. Yu, Y., Li, X., Blanchard, J., Li, Y., Iqbal, K., Liu, F., Gong, C.X., Insulin sensitizers improve learning and attenuate tau hyperphosphorylation and neuroinflammation in 3xTg-AD mice. J. Neural Transm. 122 (2015), 593–606.
103. Zhang, X.M., Cai, Y., Xiong, K., Cai, H., Luo, X.G., Feng, J.C., Clough, R.W., Struble, R.G., Patrylo, P.R., Yan, X.X., Beta-secretase-1 elevation in transgenic mouse models of Alzheimer's disease is associated with synaptic/axonal pathology and amyloidogenesis: implications for neuritic plaque development. Eur. J. Neurosci. 30 (2009), 2271–2283.
104. Zhang, Y., Zhou, B., Zhang, F., Wu, J., Hu, Y., Liu, Y., Zhai, Q., Amyloid-β induces hepatic insulin resistance by activating JAK2/STAT3/SOCS-1 signaling pathway. Diabetes 61 (2012), 1434–1443.