Prion-protein-interacting amyloid-β oligomers of high molecular weight are tightly correlated with memory impairment in multiple Alzheimer mouse models

Journal of Biological Chemistry

Volumn 290, Issue 28, 2015, Pages 17415-17438

  Kostylev, Mikhail A ^a   Kaufman, Adam C ^a   Nygaard, Haakon B ^a,b   Patel, Pujan ^a   Haas, Laura T ^a   Gunther, Erik C ^a   Vortmeyer, Alexander ^a   Strittmatter, Stephen M ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF BRITISH COLUMBIA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPROTEINS; MOLECULAR WEIGHT; OLIGOMERS; PROTEINS;

ALZHEIMER DISEASE; COGNITIVE PERFORMANCE; HIGH MOLECULAR WEIGHT; MOLECULAR CHARACTERIZATION; MOUSE MODELS; PRION PROTEIN; RELATIVE CONTRIBUTION; REPRODUCIBILITIES;

MAMMALS;

AMYLOID BETA PROTEIN; OLIGOMER; PRION PROTEIN; PRESENILIN 1; PRESENILIN 1, MOUSE; PRION; RECOMBINANT PROTEIN;

AGED; ALZHEIMER DISEASE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BEHAVIOR DISORDER; COGNITION; CONTROLLED STUDY; DISEASE COURSE; FEMALE; HUMAN; HUMAN TISSUE; LIFESPAN; MALE; MEMORY DISORDER; MOLECULAR WEIGHT; MOUSE; NONHUMAN; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN ASSEMBLY; PROTEIN BLOOD LEVEL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; ANIMAL; ANIMAL BEHAVIOR; C57BL MOUSE; CHEMISTRY; DISEASE MODEL; GENETICS; MEMORY DISORDERS; METABOLISM; MIDDLE AGED; MUTANT MOUSE STRAIN; PREFRONTAL CORTEX; PRION; PROTEIN QUATERNARY STRUCTURE; PSYCHOLOGY; TRANSGENIC MOUSE; VERY ELDERLY;

ANIMALIA; MUS;

AGED; AGED, 80 AND OVER; ALZHEIMER DISEASE; AMYLOID BETA-PEPTIDES; ANIMALS; BEHAVIOR, ANIMAL; DISEASE MODELS, ANIMAL; FEMALE; HUMANS; MALE; MEMORY DISORDERS; MICE; MICE, INBRED C57BL; MICE, MUTANT STRAINS; MICE, TRANSGENIC; MIDDLE AGED; MOLECULAR WEIGHT; PREFRONTAL CORTEX; PRESENILIN-1; PRIONS; PROTEIN STRUCTURE, QUATERNARY; PRPC PROTEINS; RECOMBINANT PROTEINS;

EID: 84940063508     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M115.643577     Document Type: Article

References (87)

1. Mayeux, R. (2003) Epidemiology of neurodegeneration. Annu. Rev. Neurosci. 26, 81-104
2. Braak, H., and Braak, E. (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol. 82, 239-259
3. Blennow, K., de Leon, M. J., and Zetterberg, H. (2006) Alzheimer's disease. Lancet 368, 387-403
4. Arendt, T. (2009) Synaptic degeneration in Alzheimer's disease. Acta Neuropathol. 118, 167-179
5. Prince, M., Bryce, R., Albanese, E., Wimo, A., Ribeiro, W., and Ferri, C. P. (2013) The global prevalence of dementia: a systematic review and meta-analysis. Alzheimer's Dementia 9, 63-75
6. Hardy, J., and Selkoe, D. J. (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297, 353-356
7. Querfurth, H. W., and LaFerla, F. M. (2010) Alzheimer's disease. N. Engl. J. Med. 362, 329-344
8. Jonsson, T., Atwal, J. K., Steinberg, S., Snaedal, J., Jonsson, P. V., Bjornsson, S., Stefansson, H., Sulem, P., Gudbjartsson, D., Maloney, J., Hoyte, K., Gustafson, A., Liu, Y., Lu, Y., Bhangale, T., et al. (2012) A mutation in APP protects against Alzheimer's disease and age-related cognitive decline. Nature 488, 96-99
9. Selkoe, D. J. (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 81, 741-766
10. Haass, C., and Selkoe, D. J. (2007) Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide. Nat. Rev. 8, 101-112
11. Reiman, E. M., Chen, K., Liu, X., Bandy, D., Yu, M., Lee, W., Ayutyanont, N., Keppler, J., Reeder, S. A., Langbaum, J. B., Alexander, G. E., Klunk, W. E., Mathis, C. A., Price, J. C., Aizenstein, H. J., et al. (2009) Fibrillar amyloid-β burden in cognitively normal people at 3 levels of genetic risk for Alzheimer's disease. Proc. Natl. Acad. Sci. U.S.A. 106, 6820-6825
12. Koffie, R. M., Meyer-Luehmann, M., Hashimoto, T., Adams, K. W., Mielke, M. L., Garcia-Alloza, M., Micheva, K. D., Smith, S. J., Kim, M. L., Lee, V. M., Hyman, B. T., and Spires-Jones, T. L. (2009) Oligomeric amyloid β associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc. Natl. Acad. Sci. U.S.A. 106, 4012-4017
13. Esparza, T. J., Zhao, H., Cirrito, J. R., Cairns, N. J., Bateman, R. J., Holtzman, D. M., and Brody, D. L. (2013) Amyloid-β oligomerization in Alzheimer dementia versus high pathology controls. Ann. Neurol. 73, 104-119
14. Savage, M. J., Kalinina, J., Wolfe, A., Tugusheva, K., Korn, R., Cash-Mason, T., Maxwell, J. W., Hatcher, N. G., Haugabook, S. J., Wu, G., Howell, B. J., Renger, J. J., Shughrue, P. J., and McCampbell, A. (2014) A sensitive Aβ oligomer assay discriminates Alzheimer's and aged control cerebrospinal fluid. J. Neurosci. 34, 2884-2897
15. Yang, T., Hong, S., O'Malley, T., Sperling, R. A., Walsh, D. M., and Selkoe, D. J. (2013) New ELISAs with high specificity for soluble oligomers of amyloid β-protein detect natural Aβ oligomers in human brain but not CSF. Alzheimer's Dementia 9, 99-112
16. Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., and Ashe, K. H. (2006) A specific amyloid-β protein assembly in the brain impairs memory. Nature 440, 352-357
17. Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., and Selkoe, D. J. (2002) Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535-539
18. Shankar, G. M., Li, S., Mehta, T. H., Garcia-Munoz, A., Shepardson, N. E., Smith, I., Brett, F. M., Farrell, M. A., Rowan, M. J., Lemere, C. A., Regan, C. M., Walsh, D. M., Sabatini, B. L., and Selkoe, D. J. (2008) Amyloid-βprotein dimers isolated directly from Alzheimer's brains impair synaptic plasticity and memory. Nat. Med. 14, 837-842
19. Takeda, S., Hashimoto, T., Roe, A. D., Hori, Y., Spires-Jones, T. L., and Hyman, B. T. (2013) Brain interstitial oligomeric amyloid β increases with age and is resistant to clearance from brain in a mouse model of Alzheimer's disease. FASEB J. 27, 3239-3248
20. Benilova, I., Karran, E., and De Strooper, B. (2012) The toxic Aβ oligomer and Alzheimer's disease: an emperor in need of clothes. Nat. Neurosci. 15, 349-357
21. Laurén, J., Gimbel, D. A., Nygaard, H. B., Gilbert, J. W., and Strittmatter, S. M. (2009) Cellular prion protein mediates impairment of synaptic plasticity by amyloid-β oligomers. Nature 457, 1128-1132
22. Chen, S., Yadav, S. P., and Surewicz, W. K. (2010) Interaction between human prion protein and amyloid-β (Aβ) oligomers: role OF N-terminal residues. J. Biol. Chem. 285, 26377-26383
23. Calella, A. M., Farinelli, M., Nuvolone, M., Mirante, O., Moos, R., Falsig, J., Mansuy, I. M., and Aguzzi, A. (2010) Prion protein and Aβ-related synaptic toxicity impairment. EMBO Mol. Med. 2, 306-314
24. Balducci, C., Beeg, M., Stravalaci, M., Bastone, A., Sclip, A., Biasini, E., Tapella, L., Colombo, L., Manzoni, C., Borsello, T., Chiesa, R., Gobbi, M., Salmona, M., and Forloni, G. (2010) Synthetic amyloid-β oligomers impair long-term memory independently of cellular prion protein. Proc. Natl. Acad. Sci. U.S.A. 107, 2295-2300
25. Freir, D. B., Nicoll, A. J., Klyubin, I., Panico, S., Mc Donald, J. M., Risse, E., Asante, E. A., Farrow, M. A., Sessions, R. B., Saibil, H. R., Clarke, A. R., Rowan, M. J., Walsh, D. M., and Collinge, J. (2011) Interaction between prion protein and toxic amyloid β assemblies can be therapeutically targeted at multiple sites. Nat. Commun. 2, 336
26. Zou, W. Q., Xiao, X., Yuan, J., Puoti, G., Fujioka, H., Wang, X., Richardson, S., Zhou, X., Zou, R., Li, S., Zhu, X., McGeer, P. L., McGeehan, J., Kneale, G., Rincon-Limas, et al. (2011) Amyloid-β42 interacts mainly with insoluble prion protein in the Alzheimer brain. J. Biol. Chem. 286, 15095-15105
27. Um, J. W., Nygaard, H. B., Heiss, J. K., Kostylev, M. A., Stagi, M., Vortmeyer, A., Wisniewski, T., Gunther, E. C., and Strittmatter, S. M. (2012) Alzheimer amyloid-β oligomer bound to postsynaptic prion protein activates Fyn to impair neurons. Nat. Neurosci. 15, 1227-1235
28. Fluharty, B. R., Biasini, E., Stravalaci, M., Sclip, A., Diomede, L., Balducci, C., La Vitola, P., Messa, M., Colombo, L., Forloni, G., Borsello, T., Gobbi, M., and Harris, D. A. (2013) An N-terminal fragment of the prion protein binds to amyloid-β oligomers and inhibits their neurotoxicity in vivo. J. Biol. Chem. 288, 7857-7866
29. Gimbel, D. A., Nygaard, H. B., Coffey, E. E., Gunther, E. C., Laurén, J., Gimbel, Z. A., and Strittmatter, S. M. (2010) Memory impairment in transgenic Alzheimer mice requires cellular prion protein. J. Neurosci. 30, 6367-6374
30. Chung, E., Ji, Y., Sun, Y., Kascsak, R. J., Kascsak, R. B., Mehta, P. D., Strittmatter, S. M., and Wisniewski, T. (2010) Anti-PrPC monoclonal antibody infusion as a novel treatment for cognitive deficits in an Alzheimer's disease model mouse. BMC Neurosci. 11, 130
31. Resenberger, U. K., Harmeier, A., Woerner, A. C., Goodman, J. L., Müller, V., Krishnan, R., Vabulas, R. M., Kretzschmar, H. A., Lindquist, S., Hartl, F. U., Multhaup, G., Winklhofer, K. F., and Tatzelt, J. (2011) The cellular prion protein mediates neurotoxic signalling of β-sheet-rich conformers independent of prion replication. EMBO J. 30, 2057-2070
32. Barry, A. E., Klyubin, I., Mc Donald, J. M., Mably, A. J., Farrell, M. A., Scott, M., Walsh, D. M., and Rowan, M. J. (2011) Alzheimer's disease brain-derived amyloid-β-mediated inhibition of LTP in vivo is prevented by immunotargeting cellular prion protein. J. Neurosci. 31, 7259-7263
33. Bate, C., and Williams, A. (2011) Amyloid-β-induced synapse damage is mediated via cross-linkage of cellular prion proteins. J. Biol. Chem. 286, 37955-37963
34. Larson, M., Sherman, M. A., Amar, F., Nuvolone, M., Schneider, J. A., Bennett, D. A., Aguzzi, A., and Lesné, S. E. (2012) The complex PrP(c)-Fyn couples human oligomeric Aβ with pathological tau changes in Alzheimer's disease. J. Neurosci. 32, 16857-16871a
35. Kudo, W., Lee, H. P., Zou, W. Q., Wang, X., Perry, G., Zhu, X., Smith, M. A., Petersen, R. B., and Lee, H. G. (2012) Cellular prion protein is essential for oligomeric amyloid-β-induced neuronal cell death. Hum. Mol. Genet. 21, 1138-1144
36. Nicoll, A. J., Panico, S., Freir, D. B., Wright, D., Terry, C., Risse, E., Herron, C. E., O'Malley, T., Wadsworth, J. D., Farrow, M. A., Walsh, D. M., Saibil, H. R., and Collinge, J. (2013) Amyloid-β nanotubes are associated with prion protein-dependent synaptotoxicity. Nat. Commun. 4, 2416
37. Um, J. W., Kaufman, A. C., Kostylev, M., Heiss, J. K., Stagi, M., Takahashi, H., Kerrisk, M. E., Vortmeyer, A., Wisniewski, T., Koleske, A. J., Gunther, E. C., Nygaard, H. B., and Strittmatter, S. M. (2013) Metabotropic glutamate receptor 5 is a coreceptor for Alzheimer Aβ oligomer bound to cellular prion protein. Neuron 79, 887-902
38. Rushworth, J. V., Griffiths, H. H., Watt, N. T., and Hooper, N. M. (2013) Prion protein-mediated toxicity of amyloid-β oligomers requires lipid rafts and the transmembrane LRP1. J. Biol. Chem. 288, 8935-8951
39. Ostapchenko, V. G., Beraldo, F. H., Mohammad, A. H., Xie, Y. F., Hirata, P. H., Magalhaes, A. C., Lamour, G., Li, H., Maciejewski, A., Belrose, J. C., Teixeira, B. L., Fahnestock, M., Ferreira, S. T., Cashman, N. R., Hajj, G. N., et al. (2013) The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid-β oligomer toxicity. J. Neurosci. 33, 16552-16564
40. Klyubin, I., Nicoll, A. J., Khalili-Shirazi, A., Farmer, M., Canning, S., Mably, A., Linehan, J., Brown, A., Wakeling, M., Brandner, S., Walsh, D. M., Rowan, M. J., and Collinge, J. (2014) Peripheral administration of a humanized anti-PrP antibody blocks Alzheimer's disease Aβ synaptotoxicity. J. Neurosci. 34, 6140-6145
41. Hu, N. W., Nicoll, A. J., Zhang, D., Mably, A. J., O'Malley, T., Purro, S. A., Terry, C., Collinge, J., Walsh, D. M., and Rowan, M. J. (2014) mGlu5 receptors and cellular prion protein mediate amyloid-β-facilitated synaptic long-term depression in vivo. Nat. Commun. 5, 3374
42. Walsh, K. P., Minamide, L. S., Kane, S. J., Shaw, A. E., Brown, D. R., Pulford, B., Zabel, M. D., Lambeth, J. D., Kuhn, T. B., and Bamburg, J. R. (2014) Amyloid-β and proinflammatory cytokines utilize a prion protein-dependent pathway to activate NADPH oxidase and induce cofilin-actin rods in hippocampal neurons. PLoS One 9, e95995
43. Dohler, F., Sepulveda-Falla, D., Krasemann, S., Altmeppen, H., Schlüter, H., Hildebrand, D., Zerr, I., Matschke, J., and Glatzel, M. (2014) High molecular mass assemblies of amyloid-β oligomers bind prion protein in patients with Alzheimer's disease. Brain 137, 873-886
44. Cissé, M., Sanchez, P. E., Kim, D. H., Ho, K., Yu, G. Q., and Mucke, L. (2011) Ablation of cellular prion protein does not ameliorate abnormal neural network activity or cognitive dysfunction in the J20 line of human amyloid precursor protein transgenic mice. J. Neurosci. 31, 10427-10431
45. Kessels, H. W., Nguyen, L. N., Nabavi, S., and Malinow, R. (2010) The prion protein as a receptor for amyloid-β. Nature 466, E3-E4
46. Vonsattel, J. P., Del Amaya, M. P., and Keller, C. E. (2008) Twenty-first century brain banking. Processing brains for research: the Columbia University methods. Acta Neuropathol. 115, 509-532
47. Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., van Belle, G., and Berg, L. (1991) The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41, 479-486
48. Braak, H., Alafuzoff, I., Arzberger, T., Kretzschmar, H., and Del Tredici, K. (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathol. 112, 389-404
49. Hyman, B. T., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Carrillo, M. C., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., Nelson, P. T., Schneider, J. A., Thal, D. R., Thies, B., et al. (2012) National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease. Alzheimer's Dementia 8, 1-13
50. Montine, T. J., Phelps, C. H., Beach, T. G., Bigio, E. H., Cairns, N. J., Dickson, D. W., Duyckaerts, C., Frosch, M. P., Masliah, E., Mirra, S. S., Nelson, P. T., Schneider, J. A., Thal, D. R., Trojanowski, J. Q., Vinters, H. V., et al. (2012) National Institute on Aging-Alzheimer's Association guidelines for the neuropathologic assessment of Alzheimer's disease: a practical approach. Acta Neuropathol. 123, 1-11
51. Hyman, B. T., and Trojanowski, J. Q. (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer disease from the National Institute on Aging and the Reagan Institute Working Group on diagnostic criteria for the neuropathological assessment of Alzheimer disease. J. Neuropathol. Exp. Neurol. 56, 1095-1097
52. National Institute on Aging, and Reagan Institute Working Group on Diagnostic Criteria for the Neuropathological Assessment of Alzheimer's Disease (1997) Consensus recommendations for the postmortem diagnosis of Alzheimer's disease. Neurobiol. Aging 18, S1-S2
53. Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., and LaFerla, F. M. (2003) Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction. Neuron 39, 409-421
54. Morris, R. (1984) Developments of a water-maze procedure for studying spatial learning in the rat. J. Neurosci. Methods 11, 47-60
55. Haas, L. T., Kostylev, M. A., and Strittmatter, S. M. (2014) Therapeutic molecules and endogenous ligands regulate the interaction between brain cellular prion protein (PrPC) and metabotropic glutamate receptor 5 (mGluR5). J. Biol. Chem. 289, 28460-28477
56. Zahn, R., Liu, A., Lührs, T., Riek, R., von Schroetter, C., López García, F., Billeter, M., Calzolai, L., Wider, G., and Wüthrich, K. (2000) NMR solution structure of the human prion protein. Proc. Natl. Acad. Sci. U.S.A. 97, 145-150
57. Shankar, G. M., Welzel, A. T., McDonald, J. M., Selkoe, D. J., and Walsh, D. M. (2011) Isolation of low-n amyloid β-protein oligomers from cultured cells, CSF, and brain. Methods Mol. Biol. 670, 33-44
58. Lalonde, R., Kim, H. D., Maxwell, J. A., and Fukuchi, K. (2005) Exploratory activity and spatial learning in 12-month-old APP(695)SWE/co+PS1/DeltaE9 mice with amyloid plaques. Neurosci. Lett. 390, 87-92
59. Garcia-Alloza, M., Robbins, E. M., Zhang-Nunes, S. X., Purcell, S. M., Betensky, R. A., Raju, S., Prada, C., Greenberg, S. M., Bacskai, B. J., and Frosch, M. P. (2006) Characterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease. Neurobiol. Dis. 24, 516-524
60. Lambert, M. P., Velasco, P. T., Chang, L., Viola, K. L., Fernandez, S., Lacor, P. N., Khuon, D., Gong, Y., Bigio, E. H., Shaw, P., De Felice, F. G., Krafft, G. A., and Klein, W. L. (2007) Monoclonal antibodies that target pathological assemblies of Aβ. J. Neurochem. 100, 23-35
61. Barghorn, S., Nimmrich, V., Striebinger, A., Krantz, C., Keller, P., Janson, B., Bahr, M., Schmidt, M., Bitner, R. S., Harlan, J., Barlow, E., Ebert, U., and Hillen, H. (2005) Globular amyloid β-peptide oligomer - a homogenous and stable neuropathological protein in Alzheimer's disease. J. Neurochem. 95, 834-847
62. 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., and Borchelt, D. R. (2004) Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase. Hum. Mol. Genet. 13, 159-170
63. Hall, A. M., and Roberson, E. D. (2012) Mouse models of Alzheimer's disease. Brain Res. Bull. 88, 3-12
64. Czech, C., and Grueninger, F. (2013) Animal models for Alzheimer's disease - the industry perspective. Drug Discov. Today 10, e73-e78
65. Hyde, L. A., Kazdoba, T. M., Grilli, M., Lozza, G., Brusa, R., Brussa, R., Zhang, Q., Wong, G. T., McCool, M. F., Zhang, L., Parker, E. M., and Higgins, G. A. (2005) Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice. Behav. Brain Res. 160, 344-355
66. Tomic, J. L., Pensalfini, A., Head, E., and Glabe, C. G. (2009) Soluble fibrillar oligomer levels are elevated in Alzheimer's disease brain and correlate with cognitive dysfunction. Neurobiol. Dis. 35, 352-358
67. Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., Berry, R., and Vassar, R. (2006) Intraneuronal β-amyloid aggregates, neurodegeneration, and neuron loss in transgenic mice with five familial Alzheimer's disease mutations: potential factors in amyloid plaque formation. J. Neurosci. 26, 10129-10140
68. Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., and Cole, G. (1996) Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice. Science 274, 99-102
69. Chen, R., Zhang, J., Wu, Y., Wang, D., Feng, G., Tang, Y.-P., Teng, Z., and Chen, C. (2012) Monoacylglycerol lipase is a therapeutic target for Alzheimer's disease. Cell Rep. 2, 1329-1339
70. Bouter, Y., Kacprowski, T., Weissmann, R., Dietrich, K., Borgers, H., Brauss, A., Sperling, C., Wirths, O., Albrecht, M., Jensen, L. R., Kuss, A. W., and Bayer, T. A. (2014) Deciphering the molecular profile of plaques, memory decline and neuron loss in two mouse models for Alzheimer's disease by deep sequencing. Front. Aging Neurosci. 6, 75
71. Loong, T. W. (2003) Understanding sensitivity and specificity with the right side of the brain. BMJ 327, 716-719
72. Dovey, H. F., John, V., Anderson, J. P., Chen, L. Z., de Saint Andrieu, P., Fang, L. Y., Freedman, S. B., Folmer, B., Goldbach, E., Holsztynska, E. J., Hu, K. L., Johnson-Wood, K. L., Kennedy, S. L., Kholodenko, D., Knops, J. E., et al. (2001) Functional γ-secretase inhibitors reduce β-amyloid peptide levels in brain. J. Neurochem. 76, 173-181
73. Cirrito, J. R., May, P. C., O'Dell, M. A., Taylor, J. W., Parsadanian, M., Cramer, J. W., Audia, J. E., Nissen, J. S., Bales, K. R., Paul, S. M., DeMattos, R. B., and Holtzman, D. M. (2003) In vivo assessment of brain interstitial fluid with microdialysis reveals plaque-associated changes in amyloid-βmetabolism and half-life. J. Neurosci. 23, 8844-8853
74. Abramowski, D., Wiederhold, K. H., Furrer, U., Jaton, A. L., Neuenschwander, A., Runser, M. J., Danner, S., Reichwald, J., Ammaturo, D., Staab, D., Stoeckli, M., Rueeger, H., Neumann, U., and Staufenbiel, M. (2008) Dynamics of Aβ turnover and deposition in different β-amyloid precursor protein transgenic mouse models following γ-secretase inhibition. J. Pharmacol. Exp. Ther. 327, 411-424
75. Chang, W. P., Huang, X., Downs, D., Cirrito, J. R., Koelsch, G., Holtzman, D. M., Ghosh, A. K., and Tang, J. (2011) β-Secretase inhibitor GRL-8234 rescues age-related cognitive decline in APP transgenic mice. FASEB J. 25, 775-784
76. Best, J. D., Smith, D. W., Reilly, M. A., O'Donnell, R., Lewis, H. D., Ellis, S., Wilkie, N., Rosahl, T. W., Laroque, P. A., Boussiquet-Leroux, C., Churcher, I., Atack, J. R., Harrison, T., and Shearman, M. S. (2007) The novel γ secretase inhibitor N-[cis-4-[(4-chlorophenyl)sulfonyl]-4-(2,5-difluorophenyl)cyclohexyl]-1,1,1-trifluoromethanesulfonamide (MRK-560) reduces amyloid plaque deposition without evidence of notch-related pathology in the Tg2576 mouse. J. Pharmacol. Exp. Ther. 320, 552-558
77. Garcia-Alloza, M., Subramanian, M., Thyssen, D., Borrelli, L. A., Fauq, A., Das, P., Golde, T. E., Hyman, B. T., and Bacskai, B. J. (2009) Existing plaques and neuritic abnormalities in APP:PS1 mice are not affected by administration of the γ-secretase inhibitor LY-411575. Mol. Neurodegener. 4, 19
78. Kayed, R., and Lasagna-Reeves, C. A. (2013) Molecular mechanisms of amyloid oligomers toxicity. J. Alzheimer's Dis. 33, S67-S78
79. Larson, M. E., and Lesné, S. E. (2012) Soluble Aβ oligomer production and toxicity. J. Neurochem. 120, 125-139
80. Bruggink, K. A., Jongbloed, W., Biemans, E. A., Veerhuis, R., Claassen, J. A., Kuiperij, H. B., and Verbeek, M. M. (2013) Amyloid-β oligomer detection by ELISA in cerebrospinal fluid and brain tissue. Anal. Biochem. 433, 112-120
81. Klaver, A. C., Patrias, L. M., Finke, J. M., and Loeffler, D. A. (2011) Specificity and sensitivity of the Aβ oligomer ELISA. J. Neurosci. Methods 195, 249-254
82. Ganzinger, K. A., Narayan, P., Qamar, S. S., Weimann, L., Ranasinghe, R. T., Aguzzi, A., Dobson, C. M., McColl, J., St George-Hyslop, P., and Klenerman, D. (2014) Single-molecule imaging reveals that small amyloid-β1-42 oligomers interact with the cellular prion protein (PrPC). ChemBioChem 15, 2515-2521
83. Karran, E., Mercken, M., and De Strooper, B. (2011) The amyloid cascade hypothesis for Alzheimer's disease: an appraisal for the development of therapeutics. Nat. Rev. Drug. Discov. 10, 698-712
84. Huang, Y., and Mucke, L. (2012) Alzheimer mechanisms and therapeutic strategies. Cell 148, 1204-1222
85. Dash, P. K., Moore, A. N., and Orsi, S. A. (2005) Blockade of γsecretase activity within the hippocampus enhances long-term memory. Biochem. Biophys. Res. Commun. 338, 777-782
86. Comery, T. A., Martone, R. L., Aschmies, S., Atchison, K. P., Diamantidis, G., Gong, X., Zhou, H., Kreft, A. F., Pangalos, M. N., Sonnenberg-Reines, J., Jacobsen, J. S., and Marquis, K. L. (2005) Acute γ-secretase inhibition improves contextual fear conditioning in the Tg2576 mouse model of Alzheimer's disease. J. Neurosci. 25, 8898-8902
87. Glabe, C. G. (2008) Structural classification of toxic amyloid oligomers. J. Biol. Chem. 283, 29639-29643