Tau deletion promotes brain insulin resistance

Journal of Experimental Medicine

Volumn 214, Issue 8, 2017, Pages 2257-2269

  Marciniak, Elodie ^a,b   Leboucher, Antoine ^a,b   Caron, Emilie ^a   Ahmed, Tariq ^c,f   Tailleux, Anne ^a   Dumont, Julie ^a,b   Issad, Tarik ^d   Gerhardt, Ellen ^e   Pagesy, Patrick ^d   Vileno, Margaux ^a,b   Bournonville, Clément ^a,b   Hamdane, Malika ^a,b   Bantubungi, Kadiombo ^a   Lancel, Steve ^a   Demeyer, Dominique ^a,b   Eddarkaoui, Sabiha ^a,b   Vallez, Emmanuelle ^a   Vieau, Didier ^a,b   Humez, Sandrine ^a,b   Faivre, Emilie ^a,b   Grenier Boley, Benjamin ^a,b   Outeiro, Tiago F ^e   Staels, Bart ^a   Amouyel, Philippe ^a,b   Balschun, Detlef ^c   Buee, Luc ^a,b   Blum, David ^a,b   more..

^a UNIV LILLE   (France)

^b Development of Innovative Strategies for a Transdisciplinary approach to ALZheimer's disease   (France)

^c UNIVERSITY OF LEUVEN   (Belgium)

^d INSTITUT COCHIN   (France)

^e UNIVERSITY MEDICAL CENTER GÖTTINGEN   (Germany)

^f HAMAD BIN KHALIFA UNIVERSITY   (Qatar)

Author keywords

[No Author keywords available]

Indexed keywords

INSULIN RECEPTOR SUBSTRATE 1; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; TAU PROTEIN; INSULIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; BRAIN; CONTROLLED STUDY; ENERGY METABOLISM; EXCITATORY POSTSYNAPTIC POTENTIAL; GLUCOSE TOLERANCE TEST; HAPLOTYPE; INSULIN RESISTANCE; LOSS OF FUNCTION MUTATION; MALE; MOUSE; NERVE CELL PLASTICITY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPLETION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; ANIMAL; C57BL MOUSE; COGNITIVE DYSFUNCTION; HIPPOCAMPUS; HUMAN; KNOCKOUT MOUSE; METABOLISM; PHYSIOLOGY;

ANIMALS; BRAIN; COGNITIVE DYSFUNCTION; HAPLOTYPES; HIPPOCAMPUS; HUMANS; INSULIN; INSULIN RESISTANCE; MALE; MICE; MICE, INBRED C57BL; MICE, KNOCKOUT; TAU PROTEINS;

EID: 85027337943     PISSN: 00221007     EISSN: 15409538     Source Type: Journal    
DOI: 10.1084/jem.20161731     Document Type: Article

References (82)

1. Ahmed, T., D. Blum, S. Burnouf, D. Demeyer, V. Buée-Scherrer, R. D'Hooge, L. Buée, and D. Balschun. 2015. Rescue of impaired late-phase longterm depression in a tau transgenic mouse model. Neurobiol. Aging. 36:730-739. http ://dx .doi .org /10 .1016 /j .neurobiolaging .2014 .09 .015
2. Arendt, T., J.T. Stieler, and M. Holzer. 2016. Tau and tauopathies. Brain Res. Bull. 126:238-292. http ://dx .doi .org /10 .1016 /j .brainresbull .2016 .08 .018
3. Barthélemy, N.R., F. Fenaille, C. Hirtz, N. Sergeant, S. Schraen-Maschke, J. Vialaret, L. Buée, A. Gabelle, C. Junot, S. Lehmann, and F. Becher. 2016. Tau protein quantification in human cerebrospinal fluid by targeted mass spectrometry at high sequence coverage provides insights into its primary structure heterogeneity. J. Proteome Res. 15:667-676. http ://dx .doi .org /10 .1021 /acs .jproteome .5b01001
4. Bomfim, T.R., L. Forny-Germano, L.B. Sathler, J. Brito-Moreira, J.-C. Houzel, H. Decker, M.A. Silverman, H. Kazi, H.M. Melo, P.L. McClean, et al. 2012. An anti-diabetes agent protects the mouse brain from defective insulin signaling caused by Alzheimer's disease-associated Aβ oligomers. J. Clin. Invest. 122:1339-1353. http ://dx .doi .org /10 .1172 /JCI57256
5. Braak, H., D.R. Thal, E. Ghebremedhin, and K. Del Tredici. 2011. Stages of the pathologic process in Alzheimer disease: Age categories from 1 to 100 years. J. Neuropathol. Exp. Neurol. 70:960-969. http ://dx .doi .org /10 .1097 /NEN .0b013e318232a379
6. Brown, L.M., D.J. Clegg, S.C. Benoit, and S.C. Woods. 2006. Intraventricular insulin and leptin reduce food intake and body weight in C57BL/6J mice. Physiol. Behav. 89:687-691. http ://dx .doi .org /10 .1016 /j .physbeh .2006 .08 .008
7. Brüning, J.C., D. Gautam, D.J. Burks, J. Gillette, M. Schubert, P.C. Orban, R. Klein, W. Krone, D. Müller-Wieland, and C.R. Kahn. 2000. Role of brain insulin receptor in control of body weight and reproduction. Science. 289:2122-2125. http ://dx .doi .org /10 .1126 /science .289 .5487 .2122
8. Burnouf, S., A. Martire, M. Derisbourg, C. Laurent, K. Belarbi, A. Leboucher, F.-J. Fernandez-Gomez, L. Troquier, S. Eddarkaoui, M.-E. Grosjean, et al. 2013. NMDA receptor dysfunction contributes to impaired brainderived neurotrophic factor-induced facilitation of hippocampal synaptic transmission in a Tau transgenic model. Aging Cell. 12:11-23. http ://dx .doi .org /10 .1111 /acel .12018
9. Clarke, J.R., N.M. Lyra E Silva, C.P. Figueiredo, R.L. Frozza, J.H. Ledo, D. Beckman, C.K. Katashima, D. Razolli, B.M. Carvalho, R. Frazão, et al. 2015. Alzheimer-associated Aβ oligomers impact the central nervous system to induce peripheral metabolic deregulation. EMBO Mol. Med. 7:190-210. http ://dx .doi .org /10 .15252 /emmm .201404183
10. Copps, K.D., and M.F. White. 2012. Regulation of insulin sensitivity by serine/threonine phosphorylation of insulin receptor substrate proteins IRS1 and IRS2. Diabetologia. 55:2565-2582. http ://dx .doi .org /10 .1007 /s00125 -012 -2644 -8
11. Cornelis, M.C., A. Flint, A.E. Field, P. Kraft, J. Han, E.B. Rimm, and R.M. van Dam. 2016. A genome-wide investigation of food addiction. Obesity (Silver Spring). 24:1336-1341. http ://dx .doi .org /10 .1002 /oby .21476
12. Coupé, B., I. Grit, P. Hulin, G. Randuineau, and P. Parnet. 2012. Postnatal growth after intrauterine growth restriction alters central leptin signal and energy homeostasis. PLoS One. 7:e30616. http ://dx .doi .org /10 .1371 /journal .pone .0030616
13. Craft, S., G. Zallen, and L.D. Baker. 1992. Glucose and memory in mild senile dementia of the Alzheimer type. J. Clin. Exp. Neuropsychol. 14:253-267. http ://dx .doi .org /10 .1080 /01688639208402827
14. Craft, S., E. Peskind, M.W. Schwartz, G.D. Schellenberg, M. Raskind, and D. Porte Jr. 1998. Cerebrospinal fluid and plasma insulin levels in Alzheimer's disease: relationship to severity of dementia and apolipoprotein E genotype. Neurology. 50:164-168. http ://dx .doi .org /10 .1212 /WNL .50 .1 .164
15. De Felice, F.G. 2013. Alzheimer's disease and insulin resistance: Translating basic science into clinical applications. J. Clin. Invest. 123:531-539. http ://dx .doi .org /10 .1172 /JCI64595
16. De Felice, F.G., and C. Benedict. 2015. A key role of insulin receptors in memory. Diabetes. 64:3653-3655. http ://dx .doi .org /10 .2337 /dbi15 -0011
17. de la Monte, S.M. 2014. Type 3 diabetes is sporadic Alzheimer's disease: Minireview. Eur. Neuropsychopharmacol. 24:1954-1960. http ://dx .doi .org /10 .1016 /j .euroneuro .2014 .06 .008
18. Dixit, R., J.L. Ross, Y.E. Goldman, and E.L.F. Holzbaur. 2008. Differential regulation of dynein and kinesin motor proteins by tau. Science. 319:1086-1089. http ://dx .doi .org /10 .1126 /science .1152993
19. Donnelly, M.P., P. Paschou, E. Grigorenko, D. Gurwitz, S.Q. Mehdi, S.L.B. Kajuna, C. Barta, S. Kungulilo, N.J. Karoma, R.-B. Lu, et al. 2010. The distribution and most recent common ancestor of the 17q21 inversion in humans. Am. J. Hum. Genet. 86:161-171. http ://dx .doi .org /10 .1016 /j .ajhg .2010 .01 .007
20. Dupuis, J., C. Langenberg, I. Prokopenko, R. Saxena, N. Soranzo, A.U. Jackson, E. Wheeler, N.L. Glazer, N. Bouatia-Naji, A.L. Gloyn, et al. MAG IC investigators. 2010. New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk. Nat. Genet. 42:105-116. http ://dx .doi .org /10 .1038 /ng .520
21. Duyckaerts, C., M. Bennecib, Y. Grignon, T. Uchihara, Y. He, F. Piette, and J.J. Hauw. 1997. Modeling the relation between neurofibrillary tangles and intellectual status. Neurobiol. Aging. 18:267-273. http ://dx .doi .org /10 .1016 /S0197 -4580(97)80306 -5
22. Fernandez, A.M., and I. Torres-Alemán. 2012. The many faces of insulin-like peptide signalling in the brain. Nat. Rev. Neurosci. 13:225-239. http ://dx .doi .org /10 .1038 /nrn3209
23. Gonçalves, S.A., J.E. Matos, and T.F. Outeiro. 2010. Zooming into protein oligomerization in neurodegeneration using BiFC. Trends Biochem. Sci. 35:643-651. http ://dx .doi .org /10 .1016 /j .tibs .2010 .05 .007
24. Grillo, C.A., K.L. Tamashiro, G.G. Piroli, S. Melhorn, J.T. Gass, R.J. Newsom, L.R. Reznikov, A. Smith, S.P. Wilson, R.R. Sakai, and L.P. Reagan. 2007. Lentivirus-mediated downregulation of hypothalamic insulin receptor expression. Physiol. Behav. 92:691-701. http ://dx .doi .org /10 .1016 /j .physbeh .2007 .05 .043
25. Grillo, C.A., G.G. Piroli, R.C. Lawrence, S.A. Wrighten, A.J. Green, S.P. Wilson, R.R. Sakai, S.J. Kelly, M.A. Wilson, D.D. Mott, and L.P. Reagan. 2015. Hippocampal insulin resistance impairs spatial learning and synaptic plasticity. Diabetes. 64:3927-3936. http ://dx .doi .org /10 .2337 / db15 -0596
26. Grober, E., D. Dickson, M.J. Sliwinski, H. Buschke, M. Katz, H. Crystal, and R.B. Lipton. 1999. Memory and mental status correlates of modified Braak staging. Neurobiol. Aging. 20:573-579. http ://dx .doi .org /10 .1016 /S0197 -4580(99)00063 -9
27. Hamdane, M., A. Bretteville, A.V. Sambo, K. Schindowski, S. Bégard, A. Delacourte, P. Bertrand, and L. Buée. 2005. p25/Cdk5-mediated retinoblastoma phosphorylation is an early event in neuronal cell death. J. Cell Sci. 118:1291-1298. http ://dx .doi .org /10 .1242 /jcs .01724
28. Harada, A., K. Oguchi, S. Okabe, J. Kuno, S. Terada, T. Ohshima, R. Sato- Yoshitake, Y. Takei, T. Noda, and N. Hirokawa. 1994. Altered microtubule organization in small-calibre axons of mice lacking tau protein. Nature. 369:488-491. http ://dx .doi .org /10 .1038 /369488a0
29. Ishii, M., and C. Iadecola. 2015. Metabolic and non-cognitive manifestations of Alzheimer's disease: The hypothalamus as both culprit and target of pathology. Cell Metab. 22:761-776. http ://dx .doi .org /10 .1016 /j .cmet .2015 .08 .016
30. Issad, T., M. Combettes, and P. Ferre. 1995. Isoproterenol inhibits insulinstimulated tyrosine phosphorylation of the insulin receptor without increasing its serine/threonine phosphorylation. Eur. J. Biochem. 234:108-115. http ://dx .doi .org /10 .1111 /j .1432 -1033 .1995 .108 c .x
31. Ittner, L.M., Y.D. Ke, F. Delerue, M. Bi, A. Gladbach, J. van Eersel, H. Wölfing, B.C. Chieng, M.J. Christie, I.A. Napier, et al. 2010. Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer's disease mouse models. Cell. 142:387-397. http ://dx .doi .org /10 .1016 /j .cell .2010 .06 .036
32. Janson, J., T. Laedtke, J.E. Parisi, P. O'Brien, R.C. Petersen, and P.C. Butler. 2004. Increased risk of type 2 diabetes in Alzheimer disease. Diabetes. 53:474-481. http ://dx .doi .org /10 .2337 /diabetes .53 .2 .474
33. Jucker, M., and L.C. Walker. 2013. Self-propagation of pathogenic protein aggregates in neurodegenerative diseases. Nature. 501:45-51. http ://dx .doi .org /10 .1038 /nature12481
34. Kimura, T., D.J. Whitcomb, J. Jo, P. Regan, T. Piers, S. Heo, C. Brown, T. Hashikawa, M. Murayama, H. Seok, et al. 2014. Microtubule-associated protein tau is essential for long-term depression in the hippocampus. Philos. Trans. R. Soc. Lond. B Biol. Sci. 369:20130144. http ://dx .doi .org /10 .1098 /rstb .2013 .0144
35. Knafo, S., C. Sánchez-Puelles, E. Palomer, I. Delgado, J.E. Draffin, J. Mingo, T. Wahle, K. Kaleka, L. Mou, I. Pereda-Perez, et al. 2016. PTEN recruitment controls synaptic and cognitive function in Alzheimer's models. Nat. Neurosci. 19:443-453. http ://dx .doi .org /10 .1038 /nn .4225
36. Lacovich, V., S.L. Espindola, M. Alloatti, V. Pozo Devoto, L.E. Cromberg, M.E. Carná, G. Forte, J.-M. Gallo, L. Bruno, G.B. Stokin, et al. 2017. Tau isoforms imbalance impairs the axonal transport of the amyloid precursor protein in human neurons. J. Neurosci. 37:58-69. http ://dx .doi .org /10 .1523 /JNE URO SCI .2305 -16 .2016
37. Lázaro, D.F., E.F. Rodrigues, R. Langohr, H. Shahpasandzadeh, T. Ribeiro, P. Guerreiro, E. Gerhardt, K. Kröhnert, J. Klucken, M.D. Pereira, et al. 2014. Systematic comparison of the effects of alpha-synuclein mutations on its oligomerization and aggregation. PLoS Genet. 10:e1004741. http ://dx .doi .org /10 .1371 /journal .pgen .1004741
38. Lei, P., S. Ayton, D.I. Finkelstein, L. Spoerri, G.D. Ciccotosto, D.K. Wright, B.X.W. Wong, P.A. Adlard, R.A. Cherny, L.Q. Lam, et al. 2012. Tau deficiency induces parkinsonism with dementia by impairing APPmediated iron export. Nat. Med. 18:291-295. http ://dx .doi .org /10 .1038 /nm .2613
39. Liu, Y., F. Liu, I. Grundke-Iqbal, K. Iqbal, and C.-X. Gong. 2011. Deficient brain insulin signalling pathway in Alzheimer's disease and diabetes. J. Pathol. 225:54-62. http ://dx .doi .org /10 .1002 /path .2912
40. Ma, J., W. Zhang, H.-F. Wang, Z.-X. Wang, T. Jiang, M.-S. Tan, J.-T. Yu, and L. Tan. 2016. Peripheral blood adipokines and insulin levels in patients with Alzheimer's disease: A replication study and metaanalysis. Curr. Alzheimer Res. 13:223-233. http ://dx .doi .org /10 .2174 /156720501303160217111434
41. Ma, Q.-L., F. Yang, E.R. Rosario, O.J. Ubeda, W. Beech, D.J. Gant, P.P. Chen, B. Hudspeth, C. Chen, Y. Zhao, et al. 2009. Beta-amyloid oligomers induce phosphorylation of tau and inactivation of insulin receptor substrate via c-Jun N-terminal kinase signaling: suppression by omega-3 fatty acids and curcumin. J. Neurosci. 29:9078-9089. http ://dx .doi .org /10 .1523 / JNE URO SCI .1071 -09 .2009
42. Ma, Q.-L., X. Zuo, F. Yang, O.J. Ubeda, D.J. Gant, M. Alaverdyan, N.C. Kiosea, S. Nazari, P.P. Chen, F. Nothias, et al. 2014. Loss of MAP function leads to hippocampal synapse loss and deficits in the Morris Water Maze with aging. J. Neurosci. 34:7124-7136. http ://dx .doi .org /10 .1523 /JNE URO SCI .3439 -13 .2014
43. Maj, M., W. Gartner, A. Ilhan, D. Neziri, J. Attems, and L. Wagner. 2010. Expression of TAU in insulin-secreting cells and its interaction with the calcium-binding protein secretagogin. J. Endocrinol. 205:25-36. http :// dx .doi .org /10 .1677 /JOE -09 -0341
44. Maj, M., G. Hoermann, S. Rasul, W. Base, L. Wagner, and J. Attems. 2016. The microtubule-associated protein tau and its relevance for pancreatic beta cells. J. Diabetes Res. 2016:1964634. http ://dx .doi .org /10 .1155 /2016 /1964634
45. Masters, C.L., G. Multhaup, G. Simms, J. Pottgiesser, R.N. Martins, and K. Beyreuther. 1985. Neuronal origin of a cerebral amyloid: neurofibrillary tangles of Alzheimer's disease contain the same protein as the amyloid of plaque cores and blood vessels. EMBO J. 4:2757-2763.
46. Mayeux, R., and Y. Stern. 2012. Epidemiology of Alzheimer disease. Cold Spring Harb. Perspect. Med. 2:a006239. http ://dx .doi .org /10 .1101 / cshperspect .a006239
47. Meneilly, G.S., and A. Hill. 1993. Alterations in glucose metabolism in patients with Alzheimer's disease. J. Am. Geriatr. Soc. 41:710-714. http :// dx .doi .org /10 .1111 /j .1532 -5415 .1993 .tb07458 .x
48. Moloney, A.M., R.J. Griffin, S. Timmons, R. O'Connor, R. Ravid, and C. O'Neill. 2010. Defects in IGF-1 receptor, insulin receptor and IRS-1/2 in Alzheimer's disease indicate possible resistance to IGF-1 and insulin signalling. Neurobiol. Aging. 31:224-243. http ://dx .doi .org /10 .1016 /j .neurobiolaging .2008 .04 .002
49. Morris, M., S. Maeda, K. Vossel, and L. Mucke. 2011. The many faces of tau. Neuron. 70:410-426. http ://dx .doi .org /10 .1016 /j .neuron .2011 .04 .009
50. Morris, M., P. Hamto, A. Adame, N. Devidze, E. Masliah, and L. Mucke. 2013. Age-appropriate cognition and subtle dopamine-independent motor deficits in aged tau knockout mice. Neurobiol. Aging. 34:1523-1529. http ://dx .doi .org /10 .1016 /j .neurobiolaging .2012 .12 .003
51. Mothe, I., and E. Van Obberghen. 1996. Phosphorylation of insulin receptor substrate-1 on multiple serine residues, 612, 632, 662, and 731, modulates insulin action. J. Biol. Chem. 271:11222-11227. http ://dx .doi .org /10 .1074 /jbc .271 .19 .11222
52. Mysoet, J., M.-H. Canu, C. Gillet, J. Fourneau, C. Garnier, B. Bastide, and E. Dupont. 2017. Reorganization of motor cortex and impairment of motor performance induced by hindlimb unloading are partially reversed by cortical IGF-1 administration. Behav. Brain Res. 317:434-443. http :// dx .doi .org /10 .1016 /j .bbr .2016 .10 .005
53. Nakatsuji, H., A. Araki, A. Hashizume, Y. Hijikata, S. Yamada, T. Inagaki, K. Suzuki, H. Banno, N. Suga, Y. Okada, et al. 2017. Correlation of insulin resistance and motor function in spinal and bulbar muscular atrophy. J. Neurol. 264:839-847. http ://dx .doi .org /10 .1007 /s00415 -017 -8405 -3
54. Neuville, P., M.T. Vanier, L. Michalik, and J.F. Launay. 1995. In situ localization with digoxigenin-labelled probes of tau-related mRNAs in the rat pancreas. Histochem. J. 27:565-574. http ://dx .doi .org /10 .1007 / BF02388454
55. Obici, S., Z. Feng, G. Karkanias, D.G. Baskin, and L. Rossetti. 2002. Decreasing hypothalamic insulin receptors causes hyperphagia and insulin resistance in rats. Nat. Neurosci. 5:566-572. http ://dx .doi .org /10 .1038 /nn0602 -861
56. Ortega-Molina, A., and M. Serrano. 2013. PTEN in cancer, metabolism, and aging. Trends Endocrinol. Metab. 24:184-189. http ://dx .doi .org /10 .1016 /j .tem .2012 .11 .002
57. Outeiro, T.F., P. Putcha, J.E. Tetzlaff, R. Spoelgen, M. Koker, F. Carvalho, B.T. Hyman, and P.J. McLean. 2008. Formation of toxic oligomeric alphasynuclein species in living cells. PLoS One. 3:e1867. (published erratum appears in PLoS One. 2008. 3:5) http ://dx .doi .org /10 .1371 /journal .pone .0001867
58. Papon, M.A., N.B. El Khoury, F. Marcouiller, C. Julien, F. Morin, A. Bretteville, F.R. Petry, S. Gaudreau, A. Amrani, P.M. Mathews, et al. 2013. Deregulation of protein phosphatase 2A and hyperphosphorylation of t protein following onset of diabetes in NOD mice. Diabetes. 62:609-617. http ://dx .doi .org /10 .2337 /db12 -0187
59. Paxinos, G., and K.B.J. Franklin. 2013. The Mouse Brain in Stereotaxic Coordinates. Academic Press Inc., Amsterdam.
60. Pierre-Eugene, C., P. Pagesy, T.T. Nguyen, M. Neuillé, G. Tschank, N. Tennagels, C. Hampe, and T. Issad. 2012. Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2. PLoS One. 7:e41992. http ://dx .doi .org /10 .1371 /journal .pone .0041992
61. Prokopenko, I., W. Poon, R. Mägi, R. Prasad B, S.A. Salehi, P. Almgren, P. Osmark, N. Bouatia-Naji, N. Wierup, T. Fall, et al. 2014. A central role for GRB10 in regulation of islet function in man. PLoS Genet. 10:e1004235. http ://dx .doi .org /10 .1371 /journal .pgen .1004235
62. Razay, G., and G.K. Wilcock. 1994. Hyperinsulinaemia and Alzheimer's disease. Age Ageing. 23:396-399. http ://dx .doi .org /10 .1093 /ageing /23 .5 .396
63. Reger, M.A., G.S. Watson, P.S. Green, C.W. Wilkinson, L.D. Baker, B. Cholerton, M.A. Fishel, S.R. Plymate, J.C.S. Breitner, W. DeGroodt, et al. 2008. Intranasal insulin improves cognition and modulates betaamyloid in early AD. Neurology. 70:440-448. (published erratum appears in Neurology. 2008. 71:866) http ://dx .doi .org /10 .1212 /01 .WNL .0000265401 .62434 .36
64. Reynolds, C.H., C.J. Garwood, S. Wray, C. Price, S. Kellie, T. Perera, M. Zvelebil, A. Yang, P.W. Sheppard, I.M. Varndell, et al. 2008. Phosphorylation regulates tau interactions with Src homology 3 domains of phosphatidylinositol 3-kinase, phospholipase Cgamma1, Grb2, and Src family kinases. J. Biol. Chem. 283:18177-18186. http ://dx .doi .org /10 .1074 /jbc .M709715200
65. Saxena, R., M.-F. Hivert, C. Langenberg, T. Tanaka, J.S. Pankow, P. Vollenweider, V. Lyssenko, N. Bouatia-Naji, J. Dupuis, A.U. Jackson, et al. MAG IC investigators. 2010. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge. Nat. Genet. 42:142-148. http ://dx .doi .org /10 .1038 /ng .521
66. Sergeant, N., A. Bretteville, M. Hamdane, M.-L. Caillet-Boudin, P. Grognet, S. Bombois, D. Blum, A. Delacourte, F. Pasquier, E. Vanmechelen, et al. 2008. Biochemistry of Tau in Alzheimer's disease and related neurological disorders. Expert Rev. Proteomics. 5:207-224. http ://dx .doi .org /10 .1586 /14789450 .5 .2 .207
67. Stanley, M., S.L. Macauley, and D.M. Holtzman. 2016a. Changes in insulin and insulin signaling in Alzheimer's disease: cause or consequence? J. Exp. Med. 213:1375-1385. http ://dx .doi .org /10 .1084 /jem .20160493
68. Stanley, M., S.L. Macauley, E.E. Caesar, L.J. Koscal, W. Moritz, G.O. Robinson, J. Roh, J. Keyser, H. Jiang, and D.M. Holtzman. 2016b. The effects of peripheral and central high insulin on brain insulin signaling and amyloid-β in young and old APP/PS1 mice. J. Neurosci. 36:11704-11715. http ://dx .doi .org /10 .1523 /JNE URO SCI .2119 -16 .2016
69. Sultan, A., F. Nesslany, M. Violet, S. Bégard, A. Loyens, S. Talahari, Z. Mansuroglu, D. Marzin, N. Sergeant, S. Humez, et al. 2011. Nuclear tau, a key player in neuronal DNA protection. J. Biol. Chem. 286:4566-4575. http ://dx .doi .org /10 .1074 /jbc .M110 .199976
70. Takeda, S., N. Sato, K. Uchio-Yamada, K. Sawada, T. Kunieda, D. Takeuchi, H. Kurinami, M. Shinohara, H. Rakugi, and R. Morishita. 2010. Diabetesaccelerated memory dysfunction via cerebrovascular inflammation and Abeta deposition in an Alzheimer mouse model with diabetes. Proc. Natl. Acad. Sci. USA. 107:7036-7041. http ://dx .doi .org /10 .1073 /pnas .1000645107
71. Talbot, K., H.-Y. Wang, H. Kazi, L.-Y. Han, K.P. Bakshi, A. Stucky, R.L. Fuino, K.R. Kawaguchi, A.J. Samoyedny, R.S. Wilson, et al. 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. http ://dx .doi .org /10 .1172 /JCI59903
72. Trabzuni, D., S. Wray, J. Vandrovcova, A. Ramasamy, R. Walker, C. Smith, C. Luk, J.R. Gibbs, A. Dillman, D.G. Hernandez, et al. 2012. MAPT expression and splicing is differentially regulated by brain region: relation to genotype and implication for tauopathies. Hum. Mol. Genet. 21:4094- 4103. http ://dx .doi .org /10 .1093 /hmg /dds238
73. Trojanowski, J.Q., and V.M.-Y. Lee. 2005. Pathological tau: A loss of normal function or a gain in toxicity? Nat. Neurosci. 8:1136-1137. http ://dx .doi .org /10 .1038 /nn0905 -1136
74. Tucker, K.L., M. Meyer, and Y.A. Barde. 2001. Neurotrophins are required for nerve growth during development. Nat. Neurosci. 4:29-37. http ://dx .doi .org /10 .1038 /82868
75. Turner, R., S. Craft, and P. Aisen. 2013. Individuals with Alzheimer's disease exhibit a high prevalence of undiagnosed impaired glucose tolerance and type 2 diabetes mellitus. Alzheimers Dement. 9:284-285. http ://dx .doi .org /10 .1016 /j .jalz .2013 .05 .573
76. Van Der Heide, L.P., A. Kamal, A. Artola, W.H. Gispen, and G.M.J. Ramakers. 2005. Insulin modulates hippocampal activity-dependent synaptic plasticity in a N-methyl-d-aspartate receptor and phosphatidyl-inositol- 3-kinase-dependent manner. J. Neurochem. 94:1158-1166. http ://dx .doi .org /10 .1111 /j .1471 -4159 .2005 .03269 .x
77. Vincent, I., M. Rosado, and P. Davies. 1996. Mitotic mechanisms in Alzheimer's disease? J. Cell Biol. 132:413-425. http ://dx .doi .org /10 .1083 /jcb .132 .3 .413
78. Violet, M., L. Delattre, M. Tardivel, A. Sultan, A. Chauderlier, R. Caillierez, S. Talahari, F. Nesslany, B. Lefebvre, E. Bonnefoy, et al. 2014. A major role for Tau in neuronal DNA and RNA protection in vivo under physiological and hyperthermic conditions. Front. Cell. Neurosci. 8:84. http ://dx .doi .org /10 .3389 /fncel .2014 .00084
79. Wang, Y., and E. Mandelkow. 2016. Tau in physiology and pathology. Nat. Rev. Neurosci. 17:5-21. http ://dx .doi .org /10 .1038 /nrn .2015 .1
80. Woods, S.C., E.C. Lotter, L.D. McKay, and D. Porte Jr. 1979. Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature. 282:503-505. http ://dx .doi .org /10 .1038 /282503a0
81. Yarchoan, M., J.B. Toledo, E.B. Lee, Z. Arvanitakis, H. Kazi, L.-Y. Han, N. Louneva, V.M.-Y. Lee, S.F. Kim, J.Q. Trojanowski, and S.E. Arnold. 2014. Abnormal serine phosphorylation of insulin receptor substrate 1 is associated with tau pathology in Alzheimer's disease and tauopathies. Acta Neuropathol. 128:679-689. http ://dx .doi .org /10 .1007 /s00401 -014 -1328 -5
82. Zhao, W.Q., F.G. De Felice, S. Fernandez, H. Chen, M.P. Lambert, M.J. Quon, G.A. Krafft, and W.L. Klein. 2008. Amyloid beta oligomers induce impairment of neuronal insulin receptors. FAS EB J. 22:246-260. http :// dx .doi .org /10 .1096 /fj .06 -7703com