Unraveling Alzheimer's: Making sense of the relationship between diabetes and Alzheimer's disease

Journal of Alzheimer's Disease

Volumn 51, Issue 4, 2016, Pages 961-977

  Schilling, Melissa A ^a  

^a NEW YORK UNIVERSITY   (United States)

Author keywords

Alzheimer disease; amylin; amyloid beta peptide; dementia; diabetes mellitus; insulin; insulysin; metalloproteases; neprilysin

Indexed keywords

ALPHA SYNUCLEIN; AMYLIN; AMYLOID BETA PROTEIN; AMYLOID PROTEIN; APOLIPOPROTEIN E4; CALHM1 PROTEIN; CATHEPSIN B; CATHEPSIN D; ENDOTHELIN CONVERTING ENZYME; GLUCOSE; INSULIN; INSULIN SENSITIZING AGENT; INSULINASE; MEMBRANE METALLOENDOPEPTIDASE; PRAMLINTIDE; PROTEIN; PROTEINASE; SOMATOMEDIN; UNCLASSIFIED DRUG; AMYLOSE;

ALLELE; ALZHEIMER DISEASE; AMNESIA; ARTICLE; BRAIN INFARCTION; COMPETITIVE INHIBITION; DISEASE ASSOCIATION; ENZYME ACTIVITY; ENZYME DEGRADATION; ENZYME SYNTHESIS; GLUCOSE INTOLERANCE; HUMAN; HYPERINSULINEMIA; INSULIN DEFICIENCY; INSULIN DEPENDENT DIABETES MELLITUS; INSULIN RELEASE; INSULIN RESISTANCE; LEARNING DISORDER; LEWY BODY; MEMORY CONSOLIDATION; MILD COGNITIVE IMPAIRMENT; MULTIINFARCT DEMENTIA; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; PRIORITY JOURNAL; SENILE PLAQUE; DIABETES MELLITUS; METABOLISM;

ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; AMYLOSE; DIABETES MELLITUS; HUMANS; INSULIN; INSULYSIN;

EID: 84964835719     PISSN: 13872877     EISSN: 18758908     Source Type: Journal    
DOI: 10.3233/JAD-150980     Document Type: Article

References (115)

1. (2015) 2015 Alzheimer's disease facts and figures. Alzheimers Dement 11, 332 - 384
2. Hurd MD, Martorell P, Delavande A, Mullen KJ, Langa KM (2013) Monetary costs of dementia in the United States. N Engl J Med 368, 1326 - 1334
3. Kavirajan H, Schneider LS (2007) Efficacy and adverse effects of cholinesterase inhibitors and memantine in vascular dementia: A meta-analysis of randomised controlled trials. Lancet Neurol 6, 782 - 792
4. Korczyn AD (2012) Why have we failed to cure Alzheimer's disease?. J Alzheimers Dis 29, 275 - 282
5. Trinh NH, Hoblyn J, Mohanty SU, Yaffe K (2003) Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease-A meta-analysis. JAMA 289, 210 - 216
6. Lanctot KL, Herrmann N, Yau KK, Khan LR, Liu BA, Loulou MM, Einarson TR (2003) Efficacy and safety of cholinesterase inhibitors in Alzheimer's disease: A meta-analysis. Can Med Assoc J 169, 557 - 564
7. Zissimopoulos J, Crimmins E, Clair P St. (2014) The value of delaying Alzheimer disease onset. Conference: Forum for Health Economics and Policy
8. de la Monte SM (2012) Brain insulin resistance and deficiency as therapeutic targets in Alzheimer's disease. Curr Alzheimer Res 9, 35 - 66
9. de la Monte SM (2012) Contributions of brain insulin resistance and deficiency in amyloid-related neurodegeneration in Alzheimer's disease. Drugs 72, 49 - 66
10. Devi L, Alldred MJ, Ginsberg SD, Ohno M (2012) Mechanisms underlying insulin deficiency-induced acceleration of beta-amyloidosis in a mouse model of Alzheimer's Disease.e. PLoS One 7, e32792
11. Wang X, Zheng W, Xie J-W, Wang T, Wang S-L, Teng W-P, Wang Z-Y (2010) Insulin deficiency exacerbates cerebral amyloidosis and behavioral deficits in an Alzheimer transgenic mouse model. Mol Neurodegener 5, 46
12. Luchsinger JA (2010) The relationship between the continuum of elevated adiposity, hyperinsulinemia, and type 2 diabetes and late-onset Alzheimer's disease: An epidemiological perspective. In Diabetes, Insulin and Alzheimer's Disease Craft S, Christen Y, eds., Springer-Verlag Berlin Heidelberg, pp. 89 - 107
13. Carantoni M, Zuliani G, Munari MR, D'Elia K, Palmieri E, Fellin R (2000) Alzheimer disease and vascular dementia: Relationships with fasting glucose and insulin levels. Dement Geriatr Cogn Disord 11, 176 - 180
14. Young SE, Mainous AG, Carnemolla M (2006) Hyperinsulinemia and cognitive decline in a middle-aged cohort. Diabetes Care 29, 2688 - 2693
15. Razay G, Wilcock GK (1994) Hyperinsulinemia and Alzheimer's disease. Age Ageing 23, 396 - 399
16. Fishel MA, Watson GS, Montine TJ, Wang Q, Green PS, Kulstad JJ, Cook DG, Peskind ER, Baker LD, Goldgaber D, Nie W, Asthana S, Plymate SR, Schwartz MW, Craft S (2005) Hyperinsulinemia provokes synchronous increases in central inflammation and beta-amyloid in normal adults. Arch Neurol 62, 1539 - 1544
17. Jackson K, Barisone G, Diaz E, Lin L, deCarli C, despa F (2013) > Amylin deposition in the brain: A second amyloid in Alzheimer disease?. Ann Neurol 74, 517 - 526
18. Srodulski S, Sharma S, Bachstetter AB, Brelsfoard JM, Pascual C, Xie XS, Saatman KE, Van Eldik LJ, Despa F (2014) Neuroinflammation and neurologic deficits in diabetes linked to brain accumulation of amylin. Mol Neurodegener 9, 30
19. Oskarsson ME, Paulsson JF, Schultz SW, Ingelsson M, Westermark P, Westermark GT (2015) In vivo seeding and cross-seeding of localized amyloidosis: A molecular link between type 2 diabetes and Alzheimer disease. Am J Pathol 185, 834 - 846
20. Lutz TA, Meyer U (2015) Amylin at the interface between metabolic and neurodegenerative disorders. Front Neurosci 9, 216
21. Adler BL, Yarchoan M, Hwang HM, Louneva N, Blair JA, Palm R, Smith MA, Lee H-g, Arnold SE, Casadesus G (2014) Neuroprotective effects of the amylin analogue pramlintide on Alzheimer's disease pathogenesis and cognition. Neurobiol Aging 35, 793 - 801
22. Qiu WQ, Au R, Zhu H, Wallack M, Liebson E, Li H, Rosenzweig J, Mwamburi M, Stern RA (2014) Positive association between plasma amylin and cognition in a homebound elderly population. J Alzheimers Dis 42, 555 - 563
23. Zhao LX, Teter B, Morihara T, Lim GP, Ambegaokar SS, Ubeda OJ, Frautschy SA, Cole GM (2004) Insulin-degrading enzyme as a downstream target of insulin receptor signaling cascade: Implications for Alzheimer's disease intervention. J Neurosci 24, 11120 - 11126
24. Jolivalt CG, Hurford R, Lee CA, Dumaop W, Rockenstein E, Masliah E (2010) Type 1 diabetes exaggerates features of Alzheimer's disease in APP transgenic mice. Exp Neurol 223, 422 - 431
25. Jiang Y, Mizisin AP, Rearden A, Jolivalt CG (2010) Diabetes induces changes in ILK, PINCH and components of related pathways in the spinal cord of rats. Brain Res 1332, 100 - 109
26. Pivovarova O, Goegebakan O, Pfeiffer AFH, Rudovich N (2009) Glucose inhibits the insulin-induced activation of the insulin-degrading enzyme in HepG2 cells. Diabetologia 52, 1656 - 1664
27. Farris W, Mansourian S, Chang Y, Lindsley L, Eckman EA, Frosch MP, Eckman CB, Tanzi RE, Selkoe DJ, Guenette S (2003) 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 100, 4162 - 4167
28. McDermott JR, Gibson AM (1997) Degradation of Alzheimer's beta-amyloid protein by human and rat brain peptidases: Involvement of insulin-degrading enzyme. Neurochem Res 22, 49 - 56
29. Qiu WQ, Borth W, Ye Z, Haass C, Teplow DB, Selkoe DJ (1996) Degradation of amyloid beta-protein by a serine protease-alpha(2)-macroglobulin complex. J Biol Chem 271, 8443 - 8451
30. Qiu WQ, Walsh DM, Ye Z, Vekrellis K, Zhang JM, Podlisny MB, Rosner MR, Safavi A, Hersh LB, Selkoe DJ (1998) Insulin-degrading enzyme regulates extracellular levels of amyloid beta-protein by degradation. J Biol Chem 273, 32730 - 32738
31. Farris W, Mansourian S, Leissring MA, Eckman EA, Bertram L, Eckman CB, Tanzi RE, Selkoe DJ (2004) Partial loss-of-function mutations in insulin-degrading enzyme that induce diabetes also impair degradation of amyloid beta-protein. Am J Pathol 164, 1425 - 1434
32. Deprez-Poulain R, Hennuyer N, Bosc D, Liang WG, Enee E, Marechal X, Charton J, Totobenazara J, Berte G, Jahklal J, Verdelet T, Dumont J, Dassonneville S, Woitrain E, Gauriot M, Paquet C, Duplan I, Hermant P, Cantrelle F-X, Sevin E, Culot M, Landry V, Herledan A, Piveteau C, Lippens G, Leroux F, Tang W-J, van Endert P, Staels B, Deprez B (2015) Catalytic site inhibition of insulin-degrading enzyme by a small molecule induces glucose intolerance in mice. Nat Commun 6, 8250
33. Perez A, Morelli L, Cresto JC, Castano EM (2000) Degradation of soluble amyloid beta-peptides 1-40, 1-42, and the Dutch variant 1-40Q by insulin degrading enzyme from Alzheimer disease and control brains. Neurochem Res 25, 247 - 255
34. Kurochkin IV (1998) Amyloidogenic determinant as a substrate recognition motif of insulin-degrading enzyme. FEBS Lett 427, 153 - 156
35. Qiu WQ, Folstein MF (2006) Insulin, insulin-degrading enzyme and amyloid-beta peptide in Alzheimer's disease: Review and hypothesis. Neurobiol Aging 27, 190 - 198
36. Bennett RG, Duckworth WC, Hamel FG (2000) Degradation of amylin by insulin-degrading enzyme. J Biol Chem 275, 36621 - 36625
37. Hardy J, Selkoe DJ (2002) Medicine-The amyloid hypothesis of Alzheimer's disease: Progress and problems on the road to therapeutics. Science 297, 353 - 356
38. Yin YI, Bassit B, Zhu L, Yang X, Wang C, Li Y-M (2007) gamma-secretase substrate concentration modulates the A beta 42/A beta 40 ratio. J Biol Chem 282, 23639 - 23644
39. Morales R, Chen B, Soto C (2009) Are amyloids infectious? In Current Hypotheses and Research Milestones in Alzheimer's Disease, Maccioni RB, Perry G, eds. Springer ScienceBusiness Media, LCC, New York, pp. 171 - 180
40. Morales R, Green KM, Soto C (2009) Cross currents in protein misfolding disorders: Interactions and therapy. CNS Neurol Disord Drug Targets 8, 363 - 371
41. Morales R, Moreno-Gonzalez I, Soto C (2013) Cross-seeding of misfolded proteins: Implications for etiology and pathogenesis of protein misfolding diseases. PLoS Pathog 9, e1003537
42. Giasson BI, Lee VMY, Trojanowski JQ (2003) Interactions of amyloidogenic proteins. Neuromolecular Med 4, 49 - 58
43. Ott A, Breteler MMB, Van Harskamp F, Grobbee DE, Hofman A (1996) Incidence of Alzheimer's disease and vascular dementia in the Rotterdam study. Neurobiol Aging 17, S79 - S79
44. Ott A, Stolk R, Van Harskamp F, Pols H, Hofman A, Breteler M (1999) Diabetes mellitus and the risk of dementia: The Rotterdam study. Neurology 10, 1937 - 1942
45. Leibson CL, Rocca WA, Hanson VA, Cha R, Kokmen E, O'Brien PC, Palumbo PJ (1997) The risk of dementia among persons with diabetes mellitus: A population-based cohort study. Ann N Y Acad Sci 826, 422 - 427
46. Peila R, Rodriguez BL, Launer LJ (2002) Type 2 diabetes, APOE gene, and the risk for dementia and related pathologies-The Honolulu-Asia Aging Study. Diabetes 51, 1256 - 1262
47. Arvanitakis Z, Wilson RS, Bienias JL, Evans DA, Bennett DA (2004) Diabetes mellitus and risk of Alzheimer disease and decline in cognitive function. Arch Neurol 61, 661 - 666
48. Luchsinger JA, Tang MX, Stern Y, Shea S, Mayeux R (2001) Diabetes mellitus and risk of Alzheimer's disease and dementia with stroke in a multiethnic cohort. Am J Epidemiol 154, 635 - 641
49. Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L (2004) Diabetes mellitus and risk of dementia in the Kungsholmen project-A 6-year follow-up study. Neurology 63, 1181 - 1186
50. Schneider JA, Arvanitakis Z, Leurgans SE, Bennett DA (2009) The neuropathology of probable Alzheimer disease and mild cognitive impairment. Ann Neurol 66, 200 - 208
51. Schneider JA, Arvanitakis Z, Bang W, Bennett DA (2007) Mixed brain pathologies account for most dementia cases in community-dwelling older persons. Neurology 69, 2197 - 2204
52. Xu WL, Qiu CX, Wahlin A, Winblad B, Fratiglioni L (2004) Diabetes mellitus and risk of dementia in the kungsholmen project: A 6-year follow-up study. Neurobiol Aging 25, S484 - S484
53. MacKnight C, Rockwood K, Awalt E, McDowell I (2002) Diabetes mellitus and the risk of dementia, Alzheimer's disease and vascular cognitive impairment in the Canadian Study of Health and Aging. Dement Geriatr Cogn Disord 14, 77 - 83
54. Fujisawa Y, Sasaki K, Akiyama K (1991) Increased insulin levels after OGTT load in peripheral blood and cerebrospinal fluid of patients with dementia of Alzheimer type. Biol Psychiatry 30, 1219 - 1228
55. Luchsinger JA, Tang MX, Shea S, Mayeux R (2004) Hyperinsulinemia and risk of Alzheimer disease. Neurology 63, 1187 - 1192
56. Craft S, Baker LD, Montine TJ, Minoshima S, Watson GS, Claxton A, Arbuckle M, Callaghan M, Tsai E, Plymate SR, Green PS, Leverenz J, Cross D, Gerton B (2012) Intranasal insulin therapy for Alzheimer disease and amnestic mild cognitive impairment a pilot clinical trial. Arch Neurol 69, 29 - 38
57. Reger MA, Watson GS, Frey WH, Baker LD, Cholerton B, Keeling ML, Belongia DA, Fishel MA, Plymate SR, Schellenberg GD, Cherrier MM, Craft S (2006) Effects of intranasal insulin on cognition in memory-impaired older adults: Modulation by APOE genotype. Neurobiol Aging 27, 451 - 458
58. Reger MA, Watson GS, Green PS, Baker LD, Cholerton B, Fishel MA, Plymate SR, Cherrier MM, Schellenberg GD, Frey WH II, Craft S (2008) Intranasal insulin administration dose-dependently modulates verbal memory and plasma amyloid-beta in memory-impaired older adults. J Alzheimers Dis 13, 323 - 331
59. Reger MA, Watson GS, Green PS, Wilkinson CW, Baker LD, Cholerton B, Fishel MA, Plymate SR, Breitner JCS, DeGroodt W, Mehta P, Craft S (2008) Intranasal insulin improves cognition and modulates beta-amyloid in early AD. Neurology 70, 440 - 448
60. Freiherr J, Hallschmid M, Frey WH II, Bruenner YF, Chapman CD, Hoelscher C, Craft S, De Felice FG, Benedict C (2013) Intranasal Insulin as a treatment for Alzheimer's disease: A review of basic research and clinical evidence. Cns Drugs 27, 505 - 514
61. Talbot K, Wang H-Y, Kazi H, Han L-Y, Bakshi KP, Stucky A, Fuino RL, Kawaguchi KR, Samoyedny AJ, Wilson RS, Arvanitakis Z, Schneider JA, Wolf BA, Bennett DA, Trojanowski JQ, Arnold SE (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
62. Zhao W-Q, Alkon DL (2001) Role of insulin and insulin receptor in learning and memory. Mol Cell Endocrinol 177, 125 - 134
63. Stern SA, Chen DY, Alberini CM (2014) The effect of insulin and insulin-like growth factors on hippocampus- and amygdala-dependent long-term memory formation. Learn Mem 21, 556 - 563
64. Chen DY, Stern SA, Garcia-Osta A, Saunier-Rebori B, Pollonini G, Bambah-Mukku D, Blitzer RD, Alberini CM (2011) A critical role for IGF-II in memory consolidation and enhancement. Nature 469, 491 - 497
65. Lupien SB, Bluhm EJ, Ishii DN (2003) Systemic insulin-like growth factor-I administration prevents cognitive impairment in diabetic rats, and brain IGF regulates learning/memory in normal adult rats. J Neurosci Res 74, 512 - 523
66. Dou J-T, Chen M, Dufour F, Alkon DL, Zhao W-Q (2005) Insulin receptor signaling in long-term memory consolidation following spatial learning. Learn Mem 12, 646 - 655
67. de la Monte SM, Wands JR (2008) Alzheimer's disease is type 3 diabetes-evidence reviewed. J Diabetes Sci Technol 2, 1101 - 1113
68. Clodfelder-Miller BJ, Zmijewska AA, Johnson GVW, Jope RS (2006) Tau is hyperphosphorylated at multiple sites in mouse brain in vivo after streptozotocin-induced insulin deficiency. Diabetes 55, 3320 - 3325
69. Rai S, Kamat PK, Nath C, Shukla R (2014) Glial activation and post-synaptic neurotoxicity: The key events in Streptozotocin (ICV) induced memory impairment in rats. Pharmacol Biochem Behav 117, 104 - 117
70. Davidson E, Coppey L, Lu B, Arballo V, Calcutt NA, Gerard C, Yorek M (2009) The roles of streptozotocin neurotoxicity and neutral endopeptidase in murine experimental diabetic neuropathy. Experimental Diabetes Research 2009, 9
71. Kochkina EG, Plesneva SA, Vasilev DS, Zhuravin IA, Turner AJ, Nalivaeva NN (2015) Effects of ageing and experimental diabetes on insulin-degrading enzyme expression in male rat tissues. Biogerontology 16, 473 - 484
72. Rezende LF, Camargo RL, Branco RCS, Cappelli APG, Boschero AC, Carneiro EM (2014) Reduced insulin clearance and lower insulin-degrading enzyme expression in the liver might contribute to the thrifty phenotype of protein-restricted mice. Br J Nutr 112, 900 - 907
73. Hamazaki H (1996) Cathepsin D is involved in the clearance of Alzheimer's β-amyloid protein. FEBS Lett 396, 139 - 142
74. McDermott JR, Gibson AM (1996) Degradation of Alzheimer's beta-amyloid protein by human cathepsin D. Neuroreport 7, 2163 - 2166
75. Saido T, Leissring MA (2012) Proteolytic degradation of amyloid beta-protein. Cold Spring Harb Perspect Med 2, a006379
76. Eckman CB, Watson M, Eckman EA (2002) Degradation of the Alzheimer's amyloid beta peptide by endothelin converting enzyme. Abstract No. 19. Soc Neurosci Abstr 19
77. Eckman EA, Eckman CB (2005) A beta-degrading enzymes: Modulators of Alzheimer's disease pathogenesis and targets for therapeutic intervention. Biochem Soc Trans 33, 1101 - 1105
78. Duckworth WC (1988) Insulin degradation: Mechanisms, products, and significance. Endocr Rev 9, 319 - 345
79. Kuo WL, Gehm BD, Rosner MR (1991) The insulin degrading enzyme regulates both intracellular and extracellular insulin levels via an insulin shunt. J Cell Biochem Suppl 78
80. Kurochkin I, Goto S (1994) Beta-amyloid peptide is specifically recognized and cleaved by insulin-degrading enzyme. Neurobiol Aging 15, S83
81. Vekrellis K, Chiu S, Mansourian S, Selkoe D (2000) Insulin-degrading enzyme is the major Abeta-degrading protease in human control and Alzheimer's disease brains. Soc Neurosci Abstr 26,. Abstract No.-588.585
82. Leissring MA, Farris W, Chang AY, Walsh DM, Wu XN, Sun XY, Frosch MP, Selkoe DJ (2003) Enhanced proteolysis of beta-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death. Neuron 40, 1087 - 1093
83. Miners JS, Barua N, Kehoe PG, Gill S, Love S (2011) A beta-Degrading Enzymes: Potential for Treatment of Alzheimer Disease. J Neuropathol Exp Neurol 70, 944 - 959
84. de Tullio MB, Morelli L, Castano EM (2008) The irreversible binding of amyloid peptide substrates to insulin-degrading enzyme A biological perspective. Prion 2, 51 - 56
85. Vingtdeux V, Chandakkar P, Zhao H, Blanc L, Ruiz S, Marambaud P (2015) CALHM1 ion channel elicits amyloid-beta clearance by insulin-degrading enzyme in cell lines and in vivo in the mouse brain. J Cell Sci 128, 2330 - 2338
86. Quan Q, Wang J, Li X, Wang Y (2013) Ginsenoside Rg1 Decreases A beta(1-42) level by upregulating PPAR gamma and IDE expression in the hippocampus of a rat model of Alzheimer's disease. PLoS One 8 e59155
87. Steneberg P, Bernardo L, Edfalk S, Lundberg L, Backlund F, Ostenson C-G, Edlund H (2013) The type 2 diabetes-associated gene ide is required for insulin secretion and suppression of alpha-synuclein levels in beta-cells. Diabetes 62, 2004 - 2014
88. Sharma SK, Chorell E, Steneberg P, Vernersson-Lindahl E, Edlund H, Wittung-Stafshede P (2015) Insulin-degrading enzyme prevents alpha-synuclein fibril formation in a nonproteolytical manner. Sci Rep 5, 12531
89. Cordes CM, Bennett RG, Siford GL, Hamel FG (2009) Nitric oxide inhibits insulin-degrading enzyme activity and function through S-nitrosylation. Biochem Pharmacol 77, 1064 - 1073
90. Pedersen WA, McMillan PJ, Kulstad JJ, Leverenz JB, Craft S, Haynatzki GR (2006) Rosiglitazone attenuates learning and memory deficits in Tg2576 Alzheimer mice. Exp Neurol 199, 265 - 273
91. Madani R, Poirier R, Wolfer DP, Welzl H, Groscurth P, Lipp H-P, Lu B, El Mouedden M, Mercken M, Nitsch RM, Mohajeri MH (2006) Lack of neprilysin suffices to generate murine amyloid-like deposits in the brain and behavioral deficit in vivo. J Neurosci Res 84, 1871 - 1878
92. Miller BC, Eckman EA, Sambamurti K, Dobbs N, Chow KM, Eckman CB, Hersh LB, Thiele DL (2003) Amyloid-beta peptide levels in brain are inversely correlated with insulysin activity levels in vivo. Proc Natl Acad Sci U S A 100, 6221 - 6226
93. Akomolafe A, Beiser A, Meigs PB, Au R, Green RC, Farrer LA, Wolf PA, Seshadri S (2006) Diabetes mellitus and risk of developing Alzheimer disease-Results from the Framingham study. Arch Neurol 63, 1551 - 1555
94. Alonso Vilatela ME, Lopez-Lopez M, Yeseas-Gomez P (2012) Genetics of Alzheimer's disease. Arch Med Res 43, 622 - 631
95. Cook DG, Leverenz JB, McMillan PJ, Kulstad JJ, Ericksen S, Roth RA, Schellenberg GD, Jin LW, Kovacina KS, Craft S (2003) Reduced hippocampal insulin-degrading enzyme in late-onset Alzheimer's disease is associated with the apolipoprotein E-epsilon 4 allele. Am J Pathol 162, 313 - 319
96. Leissring MA, Turner AJ (2013) Regulation of distinct pools of amyloid beta-protein by multiple cellular proteases. Alzheimers Res Ther 5, 37
97. Shanik MH, Xu Y, Skrha J, Dankner R, Zick Y, Roth J (2008) Insulin resistance and hyperinsulinemia: Is hyperinsulinemia the cart or the horse?. Diabetes Care 31 (Suppl 2), S262 - 268
98. Pories WJ, Dohm GL (2012) Diabetes: Have we got it all wrong? Hyperinsulinism as the culprit: Surgery provides the evidence. Diabetes Care 35, 2438 - 2442
99. Zhu H, Wang X, Wallack M, Li H, Carreras I, Dedeoglu A, Hur JY, Zheng H, Li H, Fine R, Mwamburi M, Sun X, Kowall N, Stern RA, Qiu WQ (2015) Intraperitoneal injection of the pancreatic peptide amylin potently reduces behavioral impairment and brain amyloid pathology in murine models of Alzheimer's disease. Mol Psychiatry 20, 232 - 239
100. Qiu WQ, Zhu H (2014) Amylin and its analogs: A friend or foe for the treatment of Alzheimer's disease?. Front Aging Neurosci 6, 186
101. Weyer C, Hanson R, Tataranni PA, Bogardus C, Pratley RE (2000) Fasting hyperinsulinemia predicts type 2 diabetes independent of insulin resistance: Evidence for a pathogenic role of basal insulin hypersecretion. Diabetes 49, A25 - A26
102. Leong KS, Wilding JP (1999) Obesity and diabetes. Best Pract Res Clin Endocrinol Metab 13, 221 - 237
103. Chuang YF, An Y, Bilgel M, Wong DF, Troncoso JC, O'Brien RJ, Breitner JC, Ferruci L, Resnick SM, Thambisetty M (2015) Midlife adiposity predicts earlier onset of Alzheimer's dementia, neuropathology and presymptomatic cerebral amyloid accumulation. Mol Psychiatry doi: 10.1038/mp.2015.129
104. Centers for Disease Control, and Prevention (2014) National Diabetes Statistics Report: Estimates of Diabetes and its Burden in the United States, 2014. U.S. Department of Health and Human Services Atlanta, GA
105. Leissring MA, Malito E, Hedouin S, Reinstatler L, Sahara T, Abdul-Hay SO, Choudhry S, Maharvi GM, Fauq AH, Huzarska M, May PS, Choi S, Logan TP, Turk BE, Cantley LC, Manolopoulou M, Tang WJ, Stein RL, Cuny GD, Selkoe DJ (2010) Designed inhibitors of insulin-degrading enzyme regulate the catabolism and activity of insulin. PLoS One 5, e10504
106. Shen Y, Joachimiak A, Rosner MR, Tang WJ (2006) Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism. Nature 443, 870 - 874
107. Stewart R, Liolitsa D (1999) Type 2 diabetes mellitus, cognitive impairment and dementia. Diabet Med 16, 93 - 112
108. Rivera EJ, Goldin A, Fulmer N, Tavares R, Wands JR, de la Monte SM (2005) Insulin and insulin-like growth factor expression and function deteriorate with progression of Alzheimer's disease: Link to brain reductions in acetylcholine. J Alzheimers Dis 8, 247 - 268
109. Arvanitakis Z, Schneider JA, Wilson RS, Li Y, Arnold SE, Wang Z, Bennett DA (2006) Diabetes is related to cerebral infarction but not to AD pathology in older persons. Neurology 67, 1960 - 1965
110. Kurochkin IV, Goto S (1994) Alzheimer's β-amyloid peptide specifically interacts with and is degraded by insulin degrading enzyme. FEBS Lett 345, 33 - 37
111. Qiu WQ, Ye Z, Kosik KS, Selkoe DJ (1996) Degradation of amyloid beta-protein by a secreted metalloprotease in neural and non-neural cells. Soc Neurosci Abstr 22, 1945
112. Vekrellis K, Ye Z, Qiu WQ, Walsh D, Hartley D, Chesneau V, Rosner MR, Selkoe DJ (2000) Neurons regulate extracellular levels of amyloid beta-protein via proteolysis by insulin-degrading enzyme. J Neurosci 20, 1657 - 1665
113. Abdul-Hay SO, Kang D, McBride M, Li L, Zhao J, Leissring MA (2011) Deletion of insulin-degrading enzyme elicits antipodal, age-dependent effects on glucose and insulin tolerance. PLoS One 6, e20818
114. Zhao J, Li L, Leissring M (2009) Insulin-degrading enzyme is exported via an unconventional protein secretion pathway. Mol Neurodegener 4, 1 - 5
115. Yin F, Zhang Y, Guo L, Kong S, Liu J (2012) Geniposide regulates insulin-degrading enzyme expression to inhibit the cytotoxicity of Abeta(1-42) in cortical neurons. CNS Neurol Disord Drug Targets 11, 1045 - 1051.