Metabolism of amyloid β peptide and pathogenesis of Alzheimer's disease: Towards presymptomatic diagnosis, prevention and therapy

Neuroscience Research

Volumn 54, Issue 4, 2006, Pages 235-253

  Saido, Takaomi C ^a   Iwata, Nobuhisa ^a  

^a RIKEN BRAIN SCIENCE INSTITUTE   (Japan)

Author keywords

Aging; Alzheimer's disease (AD); Amyloid peptide (A ); Metabolism; Mild cognitive impairment (MCI); Neprilysin; Proteolysis; Secretase; Vaccination

Indexed keywords

AMYLOID BETA PROTEIN; MEMBRANE METALLOENDOPEPTIDASE; SOMATOSTATIN;

AGING; ALZHEIMER DISEASE; BRAIN; COGNITIVE DEFECT; ENZYME LINKED IMMUNOSORBENT ASSAY; HUMAN; METABOLISM; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; PREVENTIVE MEDICINE; PRIORITY JOURNAL; PROTEIN DEGRADATION; REVIEW; STEADY STATE; UPREGULATION; VACCINATION;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; ANIMALS; DISEASE MODELS, ANIMAL; HUMANS;

EID: 33644853531     PISSN: 01680102     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.neures.2005.12.015     Document Type: Review

References (174)

1. H. Akiyama, S. Barger, S. Barnum, B. Bradt, J. Bauer, G.M. Cole, N.R. Cooper, P. Eikelenboom, M. Emmerling, B.L. Fiebich, C.E. Finch, S. Frautschy, W.S. Griffin, H. Hampel, M. Hull, G. Landreth, L. Lue, R. Mrak, I.R. Mackenzie, P.L. McGeer, M.K. O'Banion, J. Pachter, G. Pasinetti, C. Plata-Salaman, J. Rogers, R. Rydel, Y. Shen, W. Streit, R. Strohmeyer, I. Tooyoma, F.L. Van Muiswinkel, R. Veerhuis, D. Walker, S. Webster, B. Wegrzyniak, G. Wenk, and T. Wyss-Coray Inflammation and Alzheimer's disease Neurobiol. Aging 21 2000 383 421
2. H. Akiyama, H. Kondo, K. Ikeda, M. Kato, and P.L. McGeer Immunohistochemical localization of neprilysin in the human cerebral cortex: inverse association with vulnerability to amyloid β-protein (Aβ) deposition Brain Res. 902 2001 277 281
3. T. Asada Study on the risk factors and preventive interventions of dementing disorders Kokateki Iryogijutsuno Kakuritsu Suishin Rinshoukenkyuujigyoou 2003 Ministry of Health, Labor and Welfare of Japan pp. 1-5
4. B.J. Bacskai, S.T. Kajdasz, R.H. Christie, C. Carter, D. Games, P. Seubert, D. Schenk, and B.T. Hyman Imaging of amyloid β deposits in brains of living mice permits direct observation of clearance of plaques with immunotherapy Nat. Med. 7 2001 369 372
5. B.J. Bacskai, G.A. Hickey, J. Skoch, S.T. Kajdasz, Y. Wang, G.F. Huang, C.A. Mathis, W.E. Klunk, and B.T. Hyman Four-dimensional multiphoton imaging of brain entry, amyloid binding, and clearance of an amyloid-β ligand in transgenic mice Proc. Natl. Acad. Sci. U.S.A. 100 2003 12462 12467
6. H. Benveniste, G. Einstein, K.R. Kim, C. Hulette, and G.A. Johnson Detection of neuritic plaques in Alzheimer's disease by magnetic resonance microscopy Proc. Natl. Acad. Sci. U.S.A. 96 1999 14079 14084
7. L.M. Billings, S. Oddo, K.N. Green, J.L. McGauph, and F.M. LaFerla Interneuronal Aβ causese the onset of early Alzheimer's disease-related cognitive deficits in transgenic mice Neuron 45 2005 675 688
8. H. Braak, and E. Braak Neuropathological stageing of Alzheimer-related changes Acta Neuropathol. (Berl.) 82 1991 239 259
9. J.F. Bruno, Y. Xu, J. Song, and M. Berelowitz Molecular cloning and functional expression of a brain-specific somatostatin receptor Proc. Natl. Acad. Sci. U.S.A. 89 1992 11151 11155
10. M. Buttini, G.Q. Yu, K. Shockley, Y. Huang, B. Jones, E. Masliah, M. Mallory, T. Yeo, F.M. Longo, and L. Mucke Modulation of Alzheimer-like synaptic and cholinergic deficits in transgenic mice by human apolipoprotein E depends on isoform, aging, and overexpression of amyloid β peptides but not on plaque formation J. Neurosci. 22 2002 10539 10548
11. A. Caccamo, S. Oddo, M.C. Sugarman, Y. Akbari, and F. LaFerla Age- and region-dependent alterations in Aβ-degrading enzymes: implications for Aβ-induced disorders Neurobiol. Aging 26 2005 645 654
12. H. Cai, Y. Wang, D. McCarthy, H. Wen, D.R. Borchelt, D.L. Price, and P.C. Wong BACE1 is the major β-secretase for generation of Aβ peptides by neurons Nat. Neurosci. 4 2001 233 234
13. N.J. Cairns, V.M. Lee, and J.Q. Trojanowski The cytoskeleton in neurodegenerative diseases J. Pathol. 204 2004 438 449
14. D. Campion, C. Dumanchin, D. Hannequin, B. Dubois, S. Belliard, M. Puel, C. Thomas-Anterion, A. Michon, C. Martin, F. Charbonnier, G. Raux, A. Camuzat, C. Penet, V. Mesnage, M. Martinez, F. Clerget-Darpoux, A. Brice, and T. Frebourg Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum Am. J. Hum. Genet. 65 1999 664 670
15. R.A. Cherny, C.S. Atwood, M.E. Xilinas, D.N. Gray, W.D. Jones, C.A. McLean, K.J. Barnham, I. Volitakis, F.W. Fraser, Y. Kim, X. Huang, L.E. Goldstein, R.D. Moir, J.T. Lim, K. Beyreuther, H. Zheng, R.E. Tanzi, C.L. Masters, and A.I. Bush Treatment with a copper-zinc chelator markedly and rapidly inhibits β-amyloid accumulation in Alzheimer's disease transgenic mice Neuron 30 2001 665 676
16. M. Citron β-Secretase: progress and open questions T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 17 25 (Chapter 2)
17. J.P. Cleary, D.M. Walsh, J.J. Hofmeister, G.M. Shankar, M.A. Kuskowski, D.J. Selkoe, and K.H. Ashe Natural oligomers of the amyloid-β protein specifically disrupt cognitive function Nat. Neurosci. 8 2004 79 84
18. D.H. Cribbs, W.W. Poon, R.A. Rissman, and M. Blurton-Jones Caspase-mediated degeneration in Alzheimer's disease Am. J. Pathol. 165 2004 353 355
19. P. Davies, R. Katzman, and R.D. Terry Reduced somatostatin-like immunoreactivity in cerebral cortex from cases of Alzheimer's disease and Alzheimer senile dementia Nature 288 1980 279 280
20. R.B. DeMattos, K.R. Bales, D.J. Cummins, S.M. Paul, and D.M. Holtzman Brain to plasma amyloid-β efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease Science 295 2002 2264 2267
21. N. Demeester, C. Mertens, H. Caster, M. Goethals, J. Vandekerckhove, M. Rosseneu, and C. Labeur Comparison of the aggregation properties, secondary structure and apoptotic effects of wild-type, Flemish and Dutch N-terminally truncated amyloid β peptides Eur. J. Neurosci. 13 2001 2015 2024
22. S.A. Doggrell The potential of activation of somatostatinergic neurotransmission with FK960 in Alzheimer's disease Expert Opin. Invest. Drugs 13 2004 69 72
23. I. Dolev, and D.M. Michaelson A nontransgenic mouse model shows inducible amyloid-β (Aβ) peptide deposition and elucidates the role of apolipoprotein E in the amyloid cascade Proc. Natl. Acad. Sci. U.S.A. 101 2004 13909 13914
24. D. Dominguez, J. Tournoy, D. Hartmann, T. Huth, K. Cryns, S. Deforce, L. Serneels, I.E. Camacho, E. Marjaux, K. Craessaerts, A.J. Roebroek, M. Schwake, R. D'Hooge, P. Bach, U. Kalinke, D. Moechars, C. Alzheimer, K. Reiss, P. Saftig, and B. De Strooper Phenotypic and biochemical analyses of BACE1- and BACE2-deficient mice J. Biol. Chem. 280 2005 30797 30806
25. K. Duff, C. Eckman, C. Zehr, X. Yu, C.M. Prada, J. Perez-tur, M. Hutton, L. Buee, Y. Harigaya, D. Yager, D. Morgan, M.N. Gordon, L. Holcomb, L. Refolo, B. Zenk, J. Hardy, and S. Younkin Increased amyloid-β42(43) in brains of mice expressing mutant presenilin 1 Nature 383 1996 710 713
26. E.A. Eckman, and C.B. Eckman Aβ degradation by endothelin-converting enzymes T.C. Saido A Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 81 94 (Chapter 7)
27. E.A. Eckman, M. Watson, L. Marlow, K. Sambamurti, and C.B. Eckman Alzheimer's disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme J. Biol. Chem. 278 2003 2081 2084
28. M. Enya, M. Morishima-Kawashima, M. Yoshimura, Y. Shinkai, K. Kusui, K. Khan, D. Games, D. Schenk, S. Sugihara, H. Yamaguchi, and Y. Ihara Appearance of sodium dodecyl sulfate-stable amyloid β-protein (Aβ) dimer in the cortex during aging Am. J. Pathol. 154 1999 271 279
29. N. Ertekin-Taner, J. Ronald, L. Feuk, J. Prince, M. Tucker, L. Younkin, M. Hella, S. Jain, A. Hackett, L. Scanlin, J. Kelly, M. Kihiko-Ehman, M. Neltner, L. Hersh, M. Kindy, W. Markesbery, M. Hutton, M. de Andrade, R.C. Petersen, N. Graff-Radford, S. Estus, A.J. Brookes, and S.G. Younkin Elevated amyloid β protein (Aβ42) and late onset Alzheimer's disease are associated with single nucleotide polymorphisms in the urokinase-type plasminogen activator gene Hum. Mol. Genet. 14 2005 447 460
30. W. Farris, S. Mansourian, Y. Chang, L. Lindsley, E.A. Eckman, M.P. Frosch, C.B. Eckman, R.E. Tanzi, D.J. Selkoe, and S. Guenette Insulin-degrading enzyme regulates the levels of insulin, amyloid β-protein, and the β-amyloid precursor protein intracellular domain in vivo Proc. Natl. Acad. Sci. U.S.A. 100 2003 4162 4167
31. A. Finelli, A. Kelkar, H.-J. Song, H. Yang, and M. Konsolaki A model for studying Alzheimer's Aβ42-induced toxicity in Drosophila melanogaster Mol. Cell. Neurosci. 26 2004 365 375
32. C. Flexner Dual protease inhibitor therapy in HIV-infected patients: pharmacologic rationale and clinical benefits Annu. Rev. Pharmacol. Toxicol. 40 2000 649 674
33. C. Flicker, S.H. Ferris, and B. Reisberg Mild cognitive impairment in the elderly: predictors of dementia Neurology 41 1991 1006 1009
34. M.S. Forman, J.Q. Trojanowski, and V.M. Lee Neurodegenerative diseases: a decade of discoveries paves the way for therapeutic breakthroughs Nat. Med. 10 2004 1055 1063
35. S. Fukami, K. Watanabe, N. Iwata, J. Haraoka, B. Lu, N.P. Gerard, C. Gerard, P. Fraser, D.St. Westaway, P. George-Hyslop, and T.C. Saido Aβ-degrading endopeptidase, neprilysin, in mouse brain: synaptic and axonal localization inversely correlating with Aβ pathology Neurosci. Res. 43 2002 39 56
36. H. Funato, M. Enya, M. Yoshimura, M. Morishima-Kawashima, and Y. Ihara Presence of sodium dodecyl sulfate-stable amyloid β-protein dimers in the hippocampus CA1 not exhibiting neurofibrillary tangle formation Am. J. Pathol. 155 1999 23 28
37. H. Funato, M. Yoshimura, K. Kusui, A. Tamaoka, K. Ishikawa, N. Ohkoshi, K. Namekata, R. Okeda, and Y. Ihara Quantitation of amyloid β-protein (Aβ) in the cortex during aging and in Alzheimer's disease Am. J. Pathol. 152 1998 1633 1640
38. L. Gasparini, G.K. Gouras, R. Wang, R.S. Gross, M.F. Beal, P. Greengard, and H. Xu Stimulation of β-amyloid precursor protein trafficking by insulin reduces intraneuronal β-amyloid and requires mitogen-activated protein kinase signaling J. Neurosci. 21 2001 2561 2570
39. M.S. Goldberg, S.M. Fleming, J.J. Palacino, C. Cepeda, H.A. Lam, A. Bhatnagar, E.G. Meloni, N. Wu, L.C. Ackerson, G.J. Klapstein, M. Gajendiran, B.L. Roth, M.F. Chesselet, N.T. Maidment, M.S. Levine, and J. Shen Parkin-deficient mice exhibit nigrostriatal deficits but not loss of dopaminergic neurons J. Biol. Chem. 278 2003 43628 43635
40. J. Golomb, A. Kluger, and S.H. Ferris Mild cognitive impairment: identifying and treating the earliest stages of Alzheimer's disease Neurosci. News 3 4 2000 46 53
41. T. Gómez-Isla, J.L. Price, D.W. McKeel Jr., J.C. Morris, J.H. Growdon, and B.T. Hyman Profound loss of layer II entorhinal cortex neurons occurs in very mild Alzheimer's disease J. Neurosci. 16 1996 4491 4500
42. J. Götz, F. Chen, J. van Dorpe, and R.M. Nitsch Formation of neurofibrillary tangles in P301L tau transgenic mice induced by Aβ 42 fibrils Science 293 2001 1491 1495
43. E. Hama, K. Shirotani, N. Iwata, and T.C. Saido Effects of neprilysin chimeric proteins targeted to subcellular compartments on amyloid β peptide clearance in primary neurons J. Biol. Chem. 279 2004 30259 30264
44. E. Hama, and T.C. Saido Etiology of sporadic Alzheimer's disease: somatostatin, neprilysin, and amyloid β peptide Med. Hypotheses 65 2005 498 500
45. E. Hama, K. Shirotani, H. Masumoto, Y. Sekine-Aizawa, H. Aizawa, and T.C. Saido Clearance of extracellular and cell-associated amyloid β peptide through viral expression of neprilysin in primary neurons J. Biochem. (Tokyo) 130 2001 721 726
46. Hardy, J., 2005. http://www.alzforum.org/res/com/mut/app/default.asp; http://www.alzforum.org/res/com/mut/pre/default.asp.
47. J. Hardy, and D.J. Selkoe The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics Science 297 2002 353 356
48. D. Hartmann Functional roles of APP secretases T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 49 60 (Chapter 5)
49. M. Hayashi, A. Yamashita, and K. Shimizu Somatostatin and brain-derived neurotrophic factor mRNA expression in the primate brain: decreased levels of mRNA during aging Brain Res. 749 1997 283 289
50. W. He, and C.J. Barrow The Aβ 3-pyroglutamyl and 11-pyroglutamyl peptides found in senile plaque have greater β-sheet forming and aggregation propensities in vitro than full-length Aβ Biochemistry 38 1999 10871 10877
51. J.A. Helpern, S.P. Lee, M.F. Falangola, V.V. Dyakin, A. Bogart, B. Ardekani, K. Duff, C. Branch, T. Wisniewski, M.J. de Leon, O. Wolf, J. O'Shea, and R.A. Nixon MRI assessment of neuropathology in a transgenic mouse model of Alzheimer's disease Magn. Reson. Med. 51 2004 794 798
52. M. Higuchi, V.M. Lee, and J.Q. Trojanowski Tau and axonopathy in neurodegenerative disorders Neuromol. Med. 2 2002 131 150
53. 1H MRI detection of amyloid-β plaques in vivo Nat. Neurosci. 8 2005 527 533
54. M. Higuchi, M. Tomioka, J. Takano, K. Shirotani, N. Iwata, H. Masumoto, M. Maki, S. Itohara, and T.C. Saido Distinct mechanistic roles of calpain and caspase activation in neurodegeneration as revealed in mice over-expressing their specific inhibitors J. Biol. Chem. 280 2005 15229 15237
55. R. Hosoda, T.C. Saido, L. Otvos Jr., T. Arai, D.M. Mann, V.M. Lee, J.Q. Trojanowski, and T. Iwatsubo Quantification of modified amyloid β peptides in Alzheimer disease and Down syndrome brains J. Neuropathol. Exp. Neurol. 57 1998 1089 1095
56. K. Hsiao, P. Chapman, S. Nilsen, C. Eckman, Y. Harigaya, S. Younkin, F. Yang, and G. Cole Correlative memory deficits, Aβ elevation, and amyloid plaques in transgenic mice Science 274 1996 99 102
57. A.Y. Hsia, E. Masliah, L. McConlogue, G.Q. Yu, G. Tatsuno, K. Hu, D. Kholodenko, R.C. Malenka, R.A. Nicoll, and L. Mucke Plaque-independent disruption of neural circuits in Alzheimer's disease mouse models Proc. Natl. Acad. Sci. U.S.A. 96 1999 3228 3233
58. S. Ishiura, M. Asai, C. Hattori, N. Hotoda, B. Szabo, N. Sasagawa, and S. Tanuma APP α-secretase, a novel target for Alzheimer drug therapy T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 27 32 (Chapter 3)
59. N. Iwata, H. Mizukami, K. Shirotani, Y. Takaki, S. Muramatsu, B. Lu, N.P. Gerard, C. Gerard, K. Ozawa, and T.C. Saido Presynaptic localization of neprilysin contributes to efficient clearance of amyloid-β peptide in mouse brain J. Neurosci. 24 2004 991 998
60. N. Iwata, S. Tsubuki, E. Hama, Y. Takaki, K. Shirotani, and T.C. Saido Reply to: Clearance of amyloid β-peptide from brain: transport or metabolism? Nat. Med. 6 2000 718 719
61. 1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical and pathological deposition Nat. Med. 6 2000 143 150
62. N. Iwata, S. Tsubuki, Y. Takaki, K. Shirotani, B. Lu, N.P. Gerard, C. Gerard, E. Hama, H.J. Lee, and T.C. Saido Metabolic regulation of brain Aβ by neprilysin Science 292 2001 1550 1552
63. N. Iwata, Y. Takaki, S. Fukami, S. Tsubuki, and T.C. Saido Region-specific reduction of Aβ-degrading endopeptidase, neprilysin, in mouse hippocampus upon aging J. Neurosci. Res. 70 2002 493 500
64. N. Iwata, M. Higuchi, and T.C. Saido Metabolism of amyloid-β peptide and Alzheimer's disease Pharmacol. Ther. 108 2005 129 148
65. T. Iwatsubo, T.C. Saido, D.M. Mann, V.M. Lee, and J.Q. Trojanowski Full-length amyloid-β (1-42(43)) and amino-terminally modified and truncated amyloid-β 42(43) deposit in diffuse plaques Am. J. Pathol. 149 1996 1823 1830
66. C.R. Jack Jr., M. Garwood, T.M. Wengenack, B. Borowski, G.L. Curran, J. Lin, G. Adriany, O.H. Grohn, R. Grimm, and J.F. Poduslo In vivo visualization of Alzheimer's amyloid plaques by magnetic resonance imaging in transgenic mice without a contrast agent Magn. Reson. Med. 52 2004 1263 1271
67. J.T. Jarrett, and P.T. Lansbury Jr. Seeding "one-dimensional crystallization" of amyloid: a pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73 1993 1055 1058
68. D.D. Joshi, A. Dang, P. Yadav, J. Qian, P.S. Bandari, K. Chen, R. Donnelly, T. Castro, P. Gascon, A. Haider, and P. Rameshwar Negative feedback on the effect of stem cell factor on hematopoiesis is partly mediated through neutral endopeptidase activity on substance P: a combined functional and proteomic study Blood 98 2001 2697 2706
69. A. Kamal, A. Almenar-Queralt, J.F. LeBlanc, E.A. Roberts, and L.S. Goldstein Kinesin-mediated axonal transport of a membrane compartment containing β-secretase and presenilin-1 requires APP Nature 414 2001 643 648
70. A. Kamal, G.B. Stokin, Z. Yang, C.H. Xia, and L.S. Goldstein Axonal transport of amyloid precursor protein is mediated by direct binding to the kinesin light chain subunit of kinesin-I Neuron 28 2000 449 459
71. K. Kanemaru, T. Iwatsubo, and Y. Ihara Comparable amyloid β-protein (Aβ)42(43) and Aβ40 deposition in the aged monkey brain Neurosci. Lett. 214 1998 196 198
72. H. Kanemitsu, T. Tomiyama, and H. Mori Human neprilysin is capable of degrading amyloid β peptide not only in the monomeric form but also the pathological oligomeric form Neurosci. Lett. 350 2003 113 116
73. T. Kawarabayashi, L.H. Younkin, T.C. Saido, M. Shoji, K.H. Ashe, and S.G. Younkin Age-dependent changes in brain, CSF, and plasma amyloid β protein in the Tg2576 transgenic mouse model of Alzheimer's disease J. Neurosci. 21 2001 372 381
74. H.S. Kim, E.M. Kim, J.P. Lee, C.H. Park, S. Kim, J.H. Seo, K.A. Chang, E. Yu, S.J. Jeong, Y.H. Chong, and Y.H. Suh C-terminal fragments of amyloid precursor protein exert neurotoxicity by inducing glycogen synthase kinase-3β expression FASEB J. 17 2003 1951 1953
75. W.T. Kimberly, J.B. Zheng, S.Y. Guenette, and D.J. Selkoe The intracellular domain of the β-amyoid precursor protein is stabilized by Fe65 and translocates to the nucleus in a notch-like manner J. Biol. Chem. 276 2001 40288 40292
76. S. Kiryu-Seo, M. Sasaki, H. Yokohama, S. Nakagomi, T. Hirayama, S. Aoki, K. Wada, and H. Kiyama Damage-induced neuronal endopeptidase (DINE) is a unique metallopeptidase expressed in response to neuronal damage and activates superoxide scavengers Proc. Natl. Acad. Sci. U.S.A. 97 2000 4345 4350
77. T. Kitada, S. Asakawa, N. Hattori, H. Matsumine, Y. Yamamura, S. Minoshima, M. Yokochi, Y. Mizuno, and N. Shimizu Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism Nature 392 1998 605 608
78. S. Kitazume, Y. Tachida, R. Oka, K. Shirotani, T.C. Saido, and Y. Hashimoto Alzheimer's β-secretase, β-site amyloid precursor protein-cleaving enzyme, is responsible for cleavage secretion of a golgi-resident sialyltransferease. Proc. Natl. Acad. Sci. U.S.A. 98 2001 13554 13559
79. W.E. Klunk, H. Engler, A. Nordberg, Y. Wang, G. Blomqvist, D.P. Holt, M. Bergstrom, I. Savitcheva, G.F. Huang, S. Estrada, B. Ausen, M.L. Debnath, J. Barletta, J.C. Price, J. Sandell, B.J. Lopresti, A. Wall, P. Koivisto, G. Antoni, C.A. Mathis, and B. Langstrom Imaging brain amyloid in Alzheimer's disease with Pittsburgh compound-B Ann Neurology 55 2004 306 319
80. W.E. Klunk, B.J. Lopresti, M.D. Ikonomovic, I.M. Lefterov, R.P. Koldamova, E.E. Abrahamson, M.L. Debnath, D.P. Holt, G.F. Huang, L. Shao, S.T. DeKosky, J.C. Price, and C.A. Mathis Binding of the positron emission tomography tracer Pittsburgh compound-B reflects the amount of amyloid-β in Alzheimer's disease brain but not in transgenic mouse brain J. Neurosci. 25 2005 10598 10606
81. I. Klyubin, D.M. Walsh, C.A. Lemere, W.K. Cullen, G.M. Shankar, V. Betts, E.T. Spooner, L. Jiang, R. Anwyl, D.J. Selkoe, and M.J. Rowan Amyloid β protein immunotherapy neutralizes Aβ oligomers that disrupt synaptic plasticity in vivo Nat. Med. 11 2005 556 561
82. E.H. Koo, and R. Kopan Potential role of presenilin-regulated signaling pathways in sporadic neurodegeneration Nat. Med. 10 Suppl. 2004 S26 S30
83. M.P. Kung, C. Hou, Z.P. Zhuang, B. Zhang, D. Skovronsky, J.Q. Trojanowski, V.M. Lee, and H.F. Kung IMPY: an improved thioflavin-T derivative for in vivo labeling of β-amyloid plaques Brain Res. 956 2002 202 210
84. Y.M. Kuo, M.R. Emmerling, A.S. Woods, R.J. Cotter, and A.E. Roher Isolation, chemical characterization, and quantitation of Aβ 3-pyroglutamyl peptide from neuritic plaques and vascular amyloid deposits Biochem. Biophys. Res. Commun. 237 1997 188 191
85. Kwon, J., 2002. http://www.alzforum.org/res/com/mut/tau/default.asp.
86. M.H. Lafrance, C. Vezina, Q. Wang, G. Boileau, P. Crine, and G. Lemay Role of glycosylation in transport and enzymic activity of neutral endopeptidase-24.11 Biochem. J. 302 1994 451 454
87. O. Lazarov, G.A. Morfini, E.B. Lee, M.H. Farah, A. Szodorai, S.R. DeBoer, V.E. Koliatsos, S. Kins, V.M. Lee, P.C. Wong, D.L. Price, S.T. Brady, and S.S. Sisodia Axonal transport, amyloid precursor protein, kinesin-1, and the processing apparatus: revisited J. Neurosci. 25 2005 2386 2395
88. S.P. Lee, M.F. Falangola, R.A. Nixon, K. Duff, and J.A. Helpern Visualization of β-amyloid plaques in a transgenic mouse model of Alzheimer's disease using MR microscopy without contrast reagents Magn. Reson. Med. 52 2004 538 544
89. M.A. Leissring, W. Farris, A.Y. Chang, D.M. Walsh, X. Wu, X. Sun, M.P. Frosch, and D.J. Selkoe Enhanced proteolysis of β-amyloid in APP transgenic mice prevents plaque formation, secondary pathology, and premature death Neuron 40 2003 1087 1093
90. M.A. Leissring, M.P. Murphy, T.R. Mead, Y. Akbari, M.C. Sugarman, M. Jannatipour, B. Anliker, U. Muller, P. Saftig, B. De Strooper, M.S. Wolfe, T.E. Golde, and F.M. LaFerla A physiologic signaling role for the β-secretase-derived intracellular fragment of APP Proc. Natl. Acad. Sci. U.S.A. 99 2002 4697 4702
91. C.A. Lemere, A. Beierschmitt, M. Iglesias, E.T. Spooner, J.K. Bloom, J.F. Leverone, J.B. Zheng, T.J. Seabrook, D. Louard, D. Li, D.J. Selkoe, R.M. Palmour, and F.R. Ervin Alzheimer's disease Aβ vaccine reduces central nervous system Aβ levels in a non-human primate, the Caribbean vervet Am. J. Pathol. 165 2004 283 297
92. C.A. Lemere, F. Lopera, K.S. Kosik, C.L. Lendon, J. Ossa, T.C. Saido, H. Yamaguchi, A. Ruiz, A. Martinez, L. Madrigal, L. Hincapie, L.J.C. Arango, D.C. Anthony, E.H. Koo, A.M. Goate, D.J. Selkoe, and V.J.C. Arango The E280A Presenilin 1 mutation leads to a distinct Alzheimer's disease phenotype: Increased Aβ42 deposition and severe cerebellar pathology Nat. Med. 2 1996 1146 1150
93. J. Lewis, D.W. Dickson, W.L. Lin, L. Chisholm, A. Corral, G. Jones, S.H. Yen, N. Sahara, L. Skipper, D. Yager, C. Eckman, J. Hardy, M. Hutton, and E. McGowan Enhanced neurofibrillary degeneration in transgenic mice expressing mutant tau and APP Science 293 2001 1487 1491
94. R. Li, K. Lindholm, L.B. Yang, X. Yue, M. Citron, R. Yan, T. Beach, L. Sue, M. Sabbagh, H. Cai, P. Wong, D. Price, and Y. Shen Amyloid β peptide load is correlated with increased β-secretase activity in sporadic Alzheimer's disease patients Proc. Natl. Acad. Sci. U.S.A. 101 2004 3632 3637
95. Q. Li, and T.C. Südhof Cleavage of amyloid-β precursor protein and amyloid-β precursor-like protein by BACE1 J. Biol. Chem. 279 2004 10542 10550
96. S.F. Lichtenthaler, D. Dominguez, G.G. Westmeyer, K. Reiss, C. Haass, P. Saftig, B. De Strooper, and B. Seed The cell adhesion protein p-selectin glycoprotein ligand-1 is a substrate for the aspartyl protease BACE1 J. Biol. Chem. 278 2003 48713 48719
97. G.P. Lim, F. Calon, T. Morihara, F. Yang, B. Teter, O. Ubeda, N. Salem Jr., S.A. Frautschy, and G.M. Cole A diet enriched with the ω-3 fatty acid docosahexaenoic acid reduces amyloid burden in an aged Alzheimer mouse model J. Neurosci. 25 2005 3032 3040
98. G.P. Lim, T. Chu, F. Yang, W. Beech, S.A. Frautschy, and G.M. Cole The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse J. Neurosci. 21 2001 8370 8377
99. B. Lu, N.P. Gerard, L.F. Kolakowski Jr., M. Bozza, D. Zurakowski, O. Finco, M.C. Carroll, and C. Gerard Neutral endopeptidase modulation of septic shock J. Exp. Med. 181 1995 2271 2275
100. T. Lu, Y. Pan, S.Y. Kao, C. Li, I. Kohane, J. Chan, and B.A. Yankner Gene regulation and DNA damage in the ageing human brain Nature 429 2004 883 891
101. R.A. Marr, E. Rockenstein, A. Mukherjee, M.S. Kindy, L.B. Hersh, F.H. Gage, I.M. Verma, and E. Masliah Neprilysin gene transfer reduces human amyloid pathology in transgenic mice J. Neurosci. 23 2003 1992 1996
102. C.A. Mathis, B.J. Bacskai, S.T. Kajdasz, M.E. McLellan, M.P. Frosch, B.T. Hyman, D.P. Holt, Y. Wang, G.F. Huang, M.L. Debnath, and W.E. Klunk A lipophilic thioflavin-T derivatives for position emission tomography (PET) imaging of amyloid in brain Bioorg. Med. Chem. Lett. 12 2002 295 298
103. M.P. Mattson Cellular actions of β-amyloid precursor protein and its soluble and fibrillogenic derivatives Physiol. Rev. 77 1997 1081 1132
104. C. Mèlanie, Y. Robitalle, L. DesGroseillers, G. Boileau, and M. Marcinkiewicz Declining expression of neprilysin in Alzheimer disease vasculature: possible involvment in cerebral amyloid angiopathy J. Neuropathol. Exp. Neurol. 61 2002 849 856
105. B.C. Miller, E.A. Eckman, K. Sambamurti, N. Dobbs, K.M. Chow, C.B. Eckman, L.B. Hersh, and D.L. Thiele Amyloid-β peptide levels in brain are inversely correlated with insulysin activity levels in vivo Proc. Natl. Acad. Sci. U.S.A. 100 2003 6221 6226
106. K. Miyazaki, M. Hasegawa, K. Funahashi, and M. Umeda A metalloproteinase inhibitor domain in Alzheimer amyloid protein precursor Nature 362 1993 839 841
107. D. Moechars, I. Dewachter, K. Lorent, D. Reverse, V. Baekelandt, A. Naidu, I. Tesseur, K. Spittaels, C.V. Haute, F. Checler, E. Godaux, B. Cordell, and F. Van Leuven Early Phenotypic changes in transgenic mice that overexpress different mutants of amyloid precursor protein in brain J. Biol. Chem. 274 1999 6483 6492
108. L.N. Moller, C.E. Stidsen, B. Hartmann, and J.J. Holst Somatostatin receptors Biochim. Biophys. Acta 1616 2003 1 84
109. L. Morelli, R. Llovera, S.A. Gonzalez, J.L. Affranchino, F. Prelli, B. Frangione, J. Ghiso, and E.M. Castano Differential degradation of amyloid β genetic variants associated with hereditary dementia or stroke by insulin-degrading enzyme J. Biol. Chem. 278 2003 23221 23226
110. M. Morishima-Kawashima, N. Oshima, H. Ogata, H. Yamaguchi, M. Yoshimura, S. Sugihara, and Y. Ihara Effect of apolipoprotein E allele e4 on the initial phase of amyloid β-protein accumulation in the human brain Am. J. Pathol. 157 2000 2093 2099
111. L. Mucke, E. Masliah, G.Q. Yu, M. Mallory, E.M. Rockenstein, G. Tatsuno, K. Hu, D. Kholodenko, K. Johnson-Wood, and L. McConlogue High-level neuronal expression of Aβ1-42 in wild-type human amyloid protein precursor transgenic mice: synaptotoxicity without plaque formation J. Neurosci. 20 2000 4050 4058
112. K. Murakami, K. Irie, A. Morimoto, H. Ohigashi, M. Shindo, M. Nagao, T. Shimizu, and T. Shirasawa Synthesis, aggregation, neurotoxicity, and secondary structure of various Aβ1-42 mutants of familial Alzheimer's disease at positions 21-23 Biochem. Biophys. Res. Commun. 294 2002 5 10
113. Y. Nakano, G. Kondoh, T. Kudo, K. Imaizumi, M. Kato, J. Miyazaki, M. Tohyama, J. Takeda, and M. Takeda Accumulation of murine amyloidβ42 in a gene-dosage-dependent manner in PS1 'knock-in' mice Eur. J. Neurosci. 11 1999 2577 2581
114. C. Nilsberth, A. Westlind-Danielsson, C.B. Eckman, M.M. Condron, K. Axelman, C. Forsell, C. Stenh, J. Luthman, D.B. Teplow, S.G. Younkin, J. Naslund, and L. Lannfelt The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation Nat. Neurosci. 4 2001 887 893
115. R.A. Nixon The calpains in aging and aging-related diseases Ageing Res. Rev. 2 2003 407 418
116. A. Nordberg PET imaging of amyloid in Alzheimer's disease Lancet Neurol. 3 2004 519 527
117. N. Okamura, T. Suemoto, H. Shimadzu, M. Suzuki, T. Shiomitsu, H. Akatsu, T. Yamamoto, M. Staufenbiel, K. Yanai, H. Arai, H. Sasaki, Y. Kudo, and T. Sawada Styrylbenzoxazol derivatives for in vivo imaging of amyloid plaques in the brain J. Neurosci. 24 2004 2535 2541
118. T. Oltersdorf, L.C. Fritz, D.B. Schenk, I. Lieberburg, K.L. Johnson-Wood, E.C. Beattie, P.J. Ward, R.W. Blacher, H.F. Dovey, and S. Sinha The secreted form of the Alzheimer's amyloid precursor protein with the Kunitz domain is protease nexin-II Nature 341 1989 144 147
119. J.F. Poduslo, T.M. Wengenack, G.L. Curran, T. Wisniewski, E.M. Sigurdsson, S.I. Macura, B.J. Borowski, and C.R. Jack Jr. Molecular targeting of Alzheimer's disease amyloid plaques for contrast-enhanced magnetic resonance imaging Neurobiol. Aging 11 2002 315 329
120. B.P. Roques, F. Noble, V. Dauge, M.C. Fournie-Zaluski, and A. Beaumont Neutral endopeptidase 24.11: structure, inhibition, and experimental and clinical pharmacology Pharmacol. Rev. 45 1993 87 146
121. K.A. Roth Caspases, apoptosis, and Alzheimer disease: causation, correlation, and confusion J. Neuropathol. Exp. Neurol. 60 2001 829 838
122. C. Russo, G. Schettini, T.C. Saido, C. Hulette, C. Lippa, L. Lannfelt, B. Ghetti, P. Gambetti, M. Tabaton, and J.K. Teller Presenilin-1 mutations in Alzheimer's disease Nature 405 2000 531 532
123. T.C. Saido Alzheimer's disease as proteolytic disorders: anabolism and catabolism of β-amyloid Neurobiol. Aging 19 1998 S69 S70
124. T.C. Saido Degradation of amyloid-β peptide: a key to Alzheimer pathogeneis, prevention, and therapy Neurosci. News 5 3 2000 52 62
125. T.C. Saido Overview-Aβ metabolism: from Alzheimer research to brain aging control T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 1 16 (Chapter 1)
126. T.C. Saido, T. Iwatsubo, D.M. Mann, H. Shimada, Y. Ihara, and S. Kawashima Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques Neuron 14 1995 457 466
127. T.C. Saido, W. Yamao-Harigaya, T. Iwatsubo, and S. Kawashima Amino- and carboxyl-terminal heterogeneity of β-amyloid peptides deposited in human brain Neurosci. Lett. 215 1996 173 176
128. T.C. Saido, and H. Nakahara Proteolytic degradation of Aβ by neprilysin and other peptidases T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 61 80 (Chapter 6)
129. H.I. Sair, P.M. Doraiswamy, and J.R. Petrella In vivo amyloid imaging in Alzheimer's disease Neuroradiology 46 2004 93 104
130. K. Saito, J.S. Elce, J.E. Hamos, and R.A. Nixon Widespread activation of calcium-activated neutral proteinase (calpain) in the brain in Alzheimer disease: a potential molecular basis for neuronal degeneration Proc. Natl. Acad. Sci. U.S.A. 90 1993 2628 2632
131. T. Saito, N. Iwata, S. Tsubuki, Y. Takaki, J. Takano, S.M. Huang, T. Suemoto, M. Higuchi, and T.C. Saido Somatostatin regulates brain amyloid β peptide, Aβ42, via modulation of proteolytic degradation Nat. Med. 11 2005 434 439
132. Saito, T., Takaki, Y., Iwata, N., Trojanowski, J., Saido, T.C., 2003. Perspectives: Alzheimer's disease, neuropeptides, neuropeptidase, and amyloid-β peptide metabolism. SAGE-KE, http://sageke.sciencemag.org/cgi/ content/full/sageke;2003/3/pe1 (3) (PE1).
133. A. Saria, K.F. Hauser, H.H. Traurig, C.S. Turbek, L. Hersh, and C. Gerard Opioid-related changes in nociceptive threshold and in tissue levels of enkephalins after target disruption of the gene for neutral endopeptidase (EC 3.4.24.11) in mice Neurosci. Lett. 234 1997 27 30
134. 13C-labeled styrylbenzene derivatives for detecting brain amyloid plaques Eur. J. Med. Chem. 39 2004 573 578
135. T. Satou, B.J. Cummings, E. Head, K.A. Nielson, F.F. Hahn, N.W. Milgram, P. Velazquez, D.H. Cribbs, A.J. Tenner, and C.W. Cotman The progression of β-amyloid deposition in the frontal cortex of the aged canine Brain Res. 774 1997 35 43
136. A.M. Saundersa, M.K. Trowersb, R.A. Shimketsc, S. Blakemoreb, D.J. Crowtherb, T.A. Mansfieldc, D.M. Wallaceb, W.J. Strittmattera, and A.D. Rosesd The role of apolipoprotein E in Alzheimer's disease: pharmacogenomic target selection Biochim. Biophys. Acta 1502 2000 85 94
137. D. Schenk Amyloid-β immunotherapy for Alzheimer's disease. The end of the beginning Nat. Rev. Neurosci. 3 2003 824 828
138. D. Schenk, R. Barbour, W. Dunn, G. Gordon, H. Grajeda, T. Guido, K. Hu, J. Huang, K. Johnson-Wood, K. Khan, D. Kholodenko, M. Lee, Z. Liao, I. Lieberburg, R. Motter, L. Mutter, F. Soriano, G. Shopp, N. Vasquez, C. Vandevert, S. Walker, M. Wogulis, T. Yednock, D. Games, and P. Seubert Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse Nature 400 1999 173 177
139. D. Scheuner, C. Eckman, M. Jensen, X. Song, M. Citron, N. Suzuki, T.D. Bird, J. Hardy, M. Hutton, W. Kukull, E. Larson, E. Levy-Lahad, M. Viitanen, E. Peskind, P. Poorkaj, G. Schellenberg, R. Tanzi, W. Wasco, L. Lannfelt, D. Selkoe, and S. Younkin Secreted amyloid β-protein similar to that in the senile plaques of Alzheimer's disease is increased in vivo by the presenilin 1 and 2 and APP mutations linked to familial Alzheimer's disease Nat. Med. 2 1996 864 870
140. P. Seubert, C. Vigo-Pelfrey, F. Esch, M. Lee, H. Dovey, D. Davis, S. Sinha, M. Schlossmacher, J. Whaley, C. Swindlehurst, R. McCormack, R. Wolfert, D. Selkoe, I. Lieberburg, and D. Schenk Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids Nature 359 1992 325 327
141. H. Shimura, N. Hattori, S. Kubo, Y. Mizuno, S. Asakawa, S. Minoshima, N. Shimizu, K. Iwai, T. Chiba, K. Tanaka, and T. Suzuki Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase Nat. Genet. 25 2000 302 305
142. K. Shirotani, S. Tsubuki, N. Iwata, Y. Takaki, W. Harigaya, K. Maruyama, S. Kiryu-Seo, H. Kiyama, H. Iwata, T. Tomita, T. Iwatsubo, and T.C. Saido Neprilysin degrades both amyloid β peptides 1-40 and 1-42 most rapidly and efficiently among thiorphan- and phosphoramidon-sensitive endopeptidases J. Biol. Chem. 276 2001 21895 21901
143. K. Shirotani, S. Tsubuki, H.J. Lee, K. Maruyama, and T.C. Saido Generation of amyloid β peptide with pyroglutamate at position 3 in primary cortical neurons Neurosci. Lett. 327 2002 25 28
144. K. Shoghi-Jadid, G.W. Small, E.D. Agdeppa, V. Kepe, L.M. Ercoli, P. Siddarth, S. Read, N. Satyamurthy, A. Petric, S.C. Huang, and J.R. Barrio Localization of neurofibrillary tangles and β-amyloid plaques in the brains of living patients with Alzheimer disease Am. J. Geriatr. Psychiatry 10 2002 24 35
145. M. Shoji, T.E. Golde, J. Ghiso, T.T. Cheung, S. Estus, L.M. Shaffer, X.D. Cai, D.M. McKay, R. Tintner, B. Frangione, and S.G. Younkin Production of the Alzheimer amyloid β protein by normal proteolytic processing Science 258 1992 126 129
146. D.M. Skovronsky, B. Zhang, M.P. Kung, H.F. Kung, J.Q. Trojanowski, and V.M. Lee In vivo detection of amyloid plaques in a mouse model of Alzheimer's disease Proc. Natl. Acad. Sci. U.S.A. 97 2000 7609 7614
147. D.C. Solano, M. Sironi, C. Bonfini, S.B. Solerte, S. Govoni, and M. Racchi Insulin regulates soluble amyloid precursor protein release via phosphatidyl inositol 3 kinase-dependent pathway FASEB J. 14 2000 1015 1022
148. E. Storey, and R. Capprai The amyloid precursor protein of Alzheimer's disease and the Aβ peptide Neuropathol. Appl. Neurobiol. 25 1999 81 97
149. N. Suzuki, T.T. Cheung, X.D. Cai, A. Odaka, L. Otvos Jr., C. Eckman, T.E. Golde, and S.G. Younkin An increased percentage of long amyloid β protein secreted by familial amyloid β protein precursor (βAPP717) mutants Science 264 1994 1336 1340
150. Y. Takaki, N. Iwata, S. Tsubuki, S. Taniguchi, S. Toyoshima, B. Lu, N.P. Gerard, C. Gerard, H.J. Lee, K. Shirotani, and T.C. Saido Biochemical identification of the neutral endopeptidase family member responsible for the catabolism of amyloid β peptide in the brain J. Biochem. (Tokyo) 128 2000 897 902
151. J. Takano, M. Tomioka, T. Tsubuki, M. Higuchi, N. Iwata, S. Itohara, M. Maki, and T.C. Saido Calpain mediates excitotoxic DNA fragmentation via mitochondrial pathways: evidence from calpastatin-mutant mice J. Biol. Chem. 280 2005 16175 16184
152. T.L. Tekirian, T.C. Saido, W.R. Markesbery, M.J. Russell, D.R. Wekstein, E. Patel, and J.W. Geddes N-terminal heterogeneity of parenchymal and cerebrovascular Aβ deposits J. Neuropathol. Exp. Neurol. 57 1998 76 94
153. 11C]6-OH-BTA-1, in a transgenic mouse model of Alzheimer's disease Eur. J. Nucl. Med. Imaging 32 2005 593 600
154. S. Tsubuki, Y. Takaki, and T.C. Saido Dutch, Flemish, Italian, and Arctic mutations of APP and resistance of Aβ to physiologically relevant proteolytic degradation Lancet 361 2003 1957 1958
155. H.M. Tucker, J. Simpson, M. Kihiko-Ehmann, L.H. Younkin, J.P. McGillis, S.G. Younkin, J.L. Degen, and S. Estus Plasmin deficiency does not alter endogenous murine amyloid β levels in mice Neurosci. Lett. 368 2004 285 289
156. A.J. Turner Neprilysin second ed. A.J. Barrett N.D. Rawlings J.F. Woessner Handbook of Proteolytic Enzyzmes vol. 1 2004 Academic Press London 419 426 (Chapter 108)
157. A.J. Turner, R.E. Isaac, and D. Coates The neprilysin (NEP) family of zinc metalloendopeptidases: genomics and function Bioessays 23 2001 261 269
158. W.A. van Gool, D.B. Schenk, and P.A. Bolhuis Concentrations of amyloid-β protein in cerebrospinal fluid increase with age in patients free from neurodegenerative disease Neurosci. Lett. 172 1994 122 124
159. H. Vanderstichele, E. Van Kerschaver, C. Hesse, P. Davidsson, M.A. Buyse, N. Andreasen, L. Minthon, A. Wallin, K. Blennow, and E. Vanmechelen Standardization of measurement of β-amyloid(1-42) in cerebrospinal fluid and plasma Amyoid 7 2000 245 258
160. Y.Z. Wadghiri, E.M. Sigurdsson, M. Sadowski, J.I. Elliott, Y. Li, H. Scholtzova, C.Y. Tang, G. Aguinaldo, M. Pappolla, K. Duff, T. Wisniewski, and D.H. Turnbull Detection of Alzheimer's amyloid in transgenic mice using magnetic resonance microimaging Magn. Reson. Med. 50 2003 293 302
161. Y. Wakutani, K. Watanabe, Y. Adachi, K. Wada-Isoe, K. Urakami, H. Ninomiya, T.C. Saido, T. Hashimoto, T. Iwatsubo, and K. Nakashima Novel amyloid precursor protein gene missense mutation (D678N) in probable familial Alzheimer's disease J. Neurol. Neurosurg. Psychiatry 75 2004 1039 1042
162. D.M. Walsh, I. Klyubin, J.V. Fadeeva, W.K. Cullen, R. Anwyl, M.S. Wolfe, M.J. Rowan, and D.J. Selkoe Naturally secreted oligomers of amyloid β protein potently inhibit hippocampal long-term potentiation in vivo Nature 416 2002 535 539
163. D.-S. Wang, N. Iwata, E. Hama, T.C. Saido, and D.W. Dickson Oxidized neprilysin in aging and Alzheimer's disease brains Biochem. Biophys. Res. Commun. 310 2003 236 241
164. J. Wang, D.W. Dickson, J.Q. Trojanowski, and V.M. Lee The levels of soluble versus insoluble brain Aβ distinguish Alzheimer's disease from normal and pathologic aging Exp. Neurol. 158 1999 328 337
165. T.-L. Wang, H. Chang, C.-R. Hung, and Y.-Z. Tseng Morphine preconditioning attenuates neutrophil activation in rat models of myocardial infarction Cardiovasc. Res. 40 1998 557 563
166. M. Wolfe γ-Secretase and presenilin T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 33 47 (Chapter 4)
167. T. Wyss-Coray, F. Yan, A.H. Lin, J.D. Lambris, J.J. Alexander, R.J. Quigg, and E. Masliah Prominent neurodegeneration and increased plaque formation in complement-inhibited Alzheimer's mice Proc. Natl. Acad. Sci. U.S.A. 99 2002 10837 10842
168. N. Yamamoto, Y. Hirabayashi, M. Amari, H. Yamaguchi, G. Romanov, W.E. Van Nostrand, and K. Yanagisawa Assembly of hereditary amyloid β-protein variants in the presence of favorable gangliosides FEBS Lett. 579 2005 2185 2190
169. F. Yang, G.P. Lim, A.N. Begum, O.J. Ubeda, M.R. Simmons, S.S. Ambegaokar, P.P. Chen, R. Kayed, C.G. Glabe, S.A. Frautschy, and G.M. Cole Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo J. Biol. Chem. 280 2005 5892 58901
170. K. Yasojima, H. Akiyama, E.G. McGeer, and P.L. McGeer Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide Neurosci. Lett. 297 2001 97 100
171. K. Yasojima, E.G. McGeer, and P.L. McGeer Relationship between β amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain Brain Res. 919 2001 115 121
172. J. Zhang, P. Yarowsky, M.N. Gordon, G. Di Carlo, S. Munireddy, P.C. van Zijl, and S. Mori Detection of amyloid plaques in mouse models of Alzheimer's disease by magnetic resonance imaging Magn. Reson. Med. 51 2004 452 457
173. B.V. Zlokovic, S. Yamada, D. Holtzman, J. Ghiso, and B. Frangione Clearance of amyloid β-peptide from brain: transport or metabolism? Nat. Med. 6 2000 718
174. B.V. Zlokovic, and B. Frangione Transport-clearance hypothesis for Alzheimer's disease and potential therapeutic implications T.C. Saido Aβ Metabolism and Alzheimer's Disease 2003 Landes Bioscience Georgetown 117 125 (Chapter 10)