Anti-amyloidogenic therapies: Strategies for prevention and treatment of Alzheimer's disease

Cellular and Molecular Life Sciences

Volumn 63, Issue 13, 2006, Pages 1538-1552

  Hamaguchi, T ^a,b   Ono, K ^a   Yamada, M ^a  

^a KANAZAWA UNIVERSITY   (Japan)

^b National Hospital Organization Iou National Hospital   (Japan)

Author keywords

Alzheimer's disease; Amyloid protein; Anti amyloidognic therapy; Neprilysin; Polyphenols; Secretase

Indexed keywords

ALPHA SECRETASE; ALPHA TOCOPHEROL; AMYLOID BETA PROTEIN; AMYLOID BETA PROTEIN ANTIBODY; AMYLOID BETA PROTEIN[1-40]; AMYLOID BETA PROTEIN[1-42]; ASCORBIC ACID; BETA SECRETASE; BETA SECRETASE INHIBITOR; CATECHIN; CLIOQUINOL; CONGO RED; CURCUMIN; DOXYCYCLINE; EPICATECHIN; GAMMA SECRETASE; GAMMA SECRETASE INHIBITOR; KAEMPFEROL; MONOCLONAL ANTIBODY; MORIN; MUSCARINIC M1 RECEPTOR AGONIST; MYRICETIN; NICOTINE; NORDIHYDROGUAIARETIC ACID; POLYPHENOL; QUERCETIN; RIFAMPICIN; ROSMARINIC ACID; TANNIN; UNINDEXED DRUG;

AGING; ALZHEIMER DISEASE; BIOACCUMULATION; BRAIN TISSUE; BRAIN TOXICITY; CLINICAL TRIAL; COMPARATIVE STUDY; CONFERENCE PAPER; DOSE RESPONSE; DRUG EFFECT; DRUG MECHANISM; DRUG POTENCY; DRUG TARGETING; ENZYME ACTIVATION; ENZYME INHIBITION; ENZYME SUBSTRATE; EXPERIMENTAL MOUSE; GENE OVEREXPRESSION; HERBAL MEDICINE; HUMAN; IMMUNOREACTIVITY; IMMUNOTHERAPY; IN VITRO STUDY; INHIBITION KINETICS; MOLECULAR BIOLOGY; NEUROPATHOLOGY; NEUROPROTECTION; NONHUMAN; PASSIVE IMMUNIZATION; PROTEIN DEGRADATION; PROTEIN EXPRESSION; PROTEIN TARGETING; SMOKING; TREATMENT INDICATION; UNSPECIFIED SIDE EFFECT;

ALZHEIMER DISEASE; AMYLOID BETA-PROTEIN; AMYLOID BETA-PROTEIN PRECURSOR; ANIMALS; HUMANS; POLYMORPHISM, GENETIC;

EID: 33746649088     PISSN: 1420682X     EISSN: 15691632     Source Type: Journal    
DOI: 10.1007/s00018-005-5599-9     Document Type: Conference Paper

References (158)

1. Hardy, J. (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 20, 154-159.
2. Mattson, M. (1997) Cellular actions of beta-amyloid precursor protein and its soluble and fibrillogenic derivatives. Physiol. Rev. 77, 1081-1132.
3. Iwata, N., Tsubuki, S., Takaki, Y., Watanabe, K., Sekiguchi, M., Hosoki, E., Kawashima-Morishima, M., Lee, H. J., Hama, E., Sekine-Aizawa, Y. and Saido, T. C. (2000) Identification of the major Abeta 1-42-degrading catabolic pathway in brain parenchyma: suppression leads to biochemical pathological deposition. Nat. Med. 6, 143-150.
4. Puglielli, L., Tanzi, R. E. and Kovacs, D. M. (2003) Alzheimer's disease: the cholesterol connection. Nat. Neurosci. 6, 345-351.
5. Younkin, S. G. (1995) Evidence that A beta 42 is the real culprit in Alzheimer's disease. Ann. Neurol. 37, 287-288.
6. Selkoe, D. J. (1999) Translating cell biology into therapeutic advances in Alzheimer's disease. Nature 399: A23-A31.
7. Glenner, G. G. and Wong, C. W. (1984) Alzheimer's disease: initial report of the purification and characterization of a novel cerebrovascular amyloid protein. Biochem. Biophys. Res. Commun. 120, 885-890.
8. Glenner, G. G. and Wong, C. W. (1984) Alzheimer's disease and Down's syndrome: sharing of a unique cerebrovascular amyloid fibril protein. Biochem. Biophys. Res. Commun. 122, 1131-1135.
9. Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L. and Beyreuther, K. (1985) Amyloid plaque core protein in Alzheimer's disease and Down syndrome. Proc. Natl. Acad. Sci. USA 82, 4245-4249.
10. Kang, J., Lemaire, H. G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K. H., Multhaup, G., Beyreuther, K. and Muller-Hill, B. (1987) The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733-736.
11. Goldgaber, D., Lerman, M. I., McBride, O. W., Saffiotti, U. and Gajdusek, D. C. (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235, 877-880.
12. Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G. A., St George-Hyslop, P., Van Keuren, M. L., Patterson, D., Pagan, S., Kumit, D. M. and Neve, R. L. (1987) Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235, 880-884.
13. Robakis, N. K., Ramakrishna, N., Wolfe, G. and Wisniewski, H. M. (1987) Molecular cloning and characterization of a cDNA encoding the cerebrovascular and the neuritic plaque amyloid peptides. Proc. Natl. Acad. Sci. USA 84, 4190-4194.
14. Olson, M. I. and Shaw, C. M. (1969) Presenile dementia and Alzheimer's disease in mongolism. Brain 92, 147-156.
15. Van Broeckhoven, C., Haan, J., Bakker, E., Hardy, J. A., Van Hul, W., Wehnert, A., Vegter-Van der Vlis, M. and Roos, R. A. (1990) Amyloid beta protein precursor gene and hereditary cerebral hemorrhage with amyloidosis (Dutch). Science 248, 1120-1122.
16. Levy, E., Carman, M. D., Fernandez-Madrid, I. J., Power, M. D., Lieberburg, I., van Duinen, S. G., Bots, G. T., Luyendijk, W. and Frangione, B. (1990) Mutation of Alzheimer's disease amyloid gene in hereditary cerebral hemorrhage, Dutch type. Science 248, 1124-1126.
17. Goate, A., Chartier-Harlin, M. C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., Mant, R., Newton, P., Rooke, K., Roques, P., Talbot, C., Pericak-Vance, M., Roses, A., Williamson, R., Rossor, M., Owen, M. and Hardy, J. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704-706.
18. Hendriks, L., van Duijn, C. M., Cras, P., Cruts, M., Van Hul, W., van Harskamp, F., Warren, A., McInnis, M. G., Antonarakis, S. E., Martin, J. J., Hofman, A. and Van Broeckhoven, C. (1992) Presenile dementia and cerebral haemorrhage linked to a mutation at codon 692 of the beta-amyloid precursor protein gene. Nat. Genet. 1, 218-221.
19. Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B. and Lannfelt, L. (1992) A pathogenic mutation for probable Alzheimer's disease in the APP gene at the N-terminus of beta-amyloid. Nat. Genet. 1, 345-347.
20. 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.
21. Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., Tsuda, T., Mar, L., Foncin, J.-F., Bruni, A. C., Montesi, M. P., Sorbi, S., Rainero, I., Pinessi, L., Nee, L., Chumakov, I., Pollen, D., Brookes, A., Sanseau, P., Polinsky, R. J., Wasco, W., Da Silva, H. A. R., Haines, J. L., Pericak-Vance, M. A., Tanzi, R. E., Roses, A. D., Fraser, P. E., Rommens, J. M. and St. George-Hyslop, P. H. (1995) Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease. Nature 375, 754-760.
22. Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C. E., Jondro, P. D., Schmidt, S. D. and Wang, K. (1995) Candidate gene for the chromosome 1 familial Alzheimer's disease locus. Scienece 269, 973-977.
23. Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., Mar, L., Sorbi, S., Nacmias, B., Piacentini, S., Amaducci, L., Chumakov, I., Cohen, D., Lannfelt, L., Fraser, P. E., Rommens, J. M. and St. George-Hyslop, P. H. (1995) Familial Alzheimer's disease in kindreds with missense mutations in a gene on chromosome 1 related to the Alzheimer's disease type 3 gene. Nature 376, 775-778.
24. De Strooper, B., Saftig, P., Craessaerts, K., Vanderstichele, H., Guhde, G., Annaert, W., Von Figura, K. and Van Leuven, F. (1998) Deficiency of presenilin-1 inhibits the normal cleavage of amyloid precursor protein. Nature 391, 387-390.
25. Wolfe, M. S., Xia, W., Ostaszewski, B. L., Diehl, T. S., Kimberly, W. T. and Selkoe, D. J. (1999) Two transmembrane aspartates in presenilin-1 required for presenilin endoproteolysis and gamma-secretase activity. Nature 398, 513-517.
26. Puurkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L. et al. (1998) Tau is a candidate gene for chromosome 17 frontotemporal dementia. Ann. Neurol. 43, 815-825.
27. Hutton, M., Lendon, C.L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., Hackett, J., Adamson, J., Lincoln, S., Dickson, D., Davies, P., Petersen, R. C., Stevens, M., de Graaff, E., Wauters, E., van Baren, J., Hillebrand, M., Joosse, M., Kwon, J. M., Nowotny, P., Che, L. K., Norton, J., Morris, J. C., Reed, L. A., Trojanowski, J., Basun, H., Lannfelt, L., Neystat, M., Fahn, S., Dark, F., Tannenberg, T., Dodd, P. R., Hayward, N., Kwok, J. B., Schofield, P. R., Andreadis, A., Snowden, J., Craufurd, D., Neary, D., Owen, F., Oostra, B. A., Hardy, J., Goate, A., van Swieten, J., Mann, D., Lynch, T. and Heutink, P. (1998) Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 393, 702-705.
28. Hardy, J., Duff, K., Hardy, K. G., Perez-Tur, J. and Hutton, M. (1998) Genetic dissection of Alzheimer's disease and related dementias: amyloid and its relationship to tau. Nat. Neurosci. 1, 355-358.
29. Miller, D. L., Papayannopoulos, I. A., Styles, J., Bobin, S. A., Lin, Y. Y., Biemann, K. and Iqbal, K. (1993) Peptide compositions of the cerebrovascular and senile plaque core amyloid deposits of Alzheimer's disease. Arch. Biochem. Biophys. 301, 41-52.
30. Roher, A. E., Lowenson, J. D., Clarke, S., Woods, A. S., Cotter, R. J., Gowing, E. and Ball, M. J. (1993) beta-Amyloid-(1-42) is a major component of cerebrovascular amyloid deposits: implications for the pathology of Alzheimer disease. Proc. Natl. Acad. Sci. USA 90, 10836-10840.
31. Iwatsubo, T., Odaka, A., Suzuki, N., Muzusawa, H. and Ihara, Y. (1994) Visualization of A beta 42 (43) and A beta 40 in senile plaques with end-specific A beta monoclonals: evidence that an initially deposited species is A beta 42 (43). Neuron 13, 45-53.
32. Golde, T. E., Eckman, C. B. and Youkin, S. G. (2000) Biochemical detection of Abeta isoforms: implications for pathogenesis, diagnosis, and treatment of Alzheimer's disease. Biochim. Biophys. Acta 1502, 172-187.
33. Lemere, C. A., Blusztajn, J. K., Yamaguchi, H., Wisniewski, T., Saido, T. C. and Selkoe, D. J. (1996) Sequence of deposition of heterogeneous amyloid beta-peptides and APO E in Down syndrome: implications for initial events in amyloid plaque formation. Neurobiol. Dis. 3, 16-32.
34. Jarrett, J. T., Berger, E. P., Lansbury, P. T. Jr. (1993) The carboxy terminus of β amyloid protein is critical for the seeding of amyloid formation: implications for the pathogenesis of Alzheimer's disease. Biochemistry 32, 4693-4697.
35. McGowan, E., Pickford F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., Jansen, K., Delucia, M., Lin, W. L., Dolios, G., Wang, R., Eckman, C. B., Dickson, D. W., Hutton, M., Hardy, J. and Golde, T. (2005) Aβ42 is essential for parenchymal and vascular amyloid deposition in mice. Neuron 47, 191-199.
36. Vassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., Luo, Y., Fisher, S., Fuller, J., Edenson, S., Lile, J., Jarosinski, M. A., Biere, A. L., Curran, E., Burgess, T., Louis, J. C., Collins, F., Treanor, J., Rogers, G. and Citron, M. (1999) Beta-secretase cleavage of Alzheimer's amyloid precursor protein by the transmembrane aspartic protease BACE. Science 286, 735-741.
37. Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashier, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., Carter, D. B., Tomasselli, A. G., Parodi, L. A., Heinrikson, R. L. and Gumey, M. E. (1999) Membrane-anchored aspartyl protease with Alzheimer's disease beta-secretase activity. Nature 402, 533-537.
38. Sinha, S., Anderson, J. P., Barbour, R., Basi, G. S., Caccavello, R., Davis, D., Doan, M., Dovey, H. F., Frigon, N., Hong, J., Jacobson-Croak, K., Jewett, N., Keim, P., Knops, J., Lieberburg, I., Power, M., Tatsuno, G., Tung, J., Schenk, D., Seubert, P., Suomensaari, S. M., Wang, S., Walker, D., Zhao, J., McConlogue, L. and John, V. (1999) Purification and cloning of amyloid precursor protein beta-secretase from human brain. Nature 402, 537-540.
39. Hussain, I., Powell, D., Howlett, D. R., Tew, D. G., MeekT. D., Chapman, C., Gloger, I. S., Murphy, K. E., Southan, C. D., Ryan, D. M., Smith, T. S., Simmons, D. L., Walsh, F. S., Dingwall, C. and Christie, G. (1999) Identification of a novel aspartic protease (Asp 2) as beta-secretase. Mol. Cell Neurosci. 14, 419-427.
40. Saunders, A. J., Kim, T. and Tanzi, R. E. (1999) BACE maps to chromosome 11 and a BACE homolog, BACE2, reside in the obligate Down syndrome region of chromosome 21. Science 286, 1255-1256.
41. Luo, Y., Bolon, B., Kahn, S., Bennett, B. D., Babu-Khan, S., Denis, P., Fan, W., Kha, H., Zhang, J., Gong, Y., Martin, L., Louis, J. C., Yan, Q., Richards, W. G., Citron, M. and Vassar, R. (2001) Mice deficient in BACE1, the Alzheimer's beta-secretase, have normal phenotype and abolished beta-amyloid generation. Nat. Neurosci. 4, 231-232.
42. Cai, H., Wang, Y., McCarthy, D., Wen, H., Borchelt, D. R., Price, D. L. and Wong, P. C. (2001) BACE1 is the major beta-secretase for generation of Abeta peptides by neurons. Nat. Neurosci. 4, 233-234.
43. Roberds, S. L., Anderson, J., Basi, G., Bienkowski, M. J., Branstetter, D. G., Chen, K. S., Freedman, S. B., Frigon, N. L., Games, D., Hu, K., Johnson-Wood, K., Kappenman, K. E., Kawabe, T. T., Kola, I., Kuehn, R., Lee, M., Liu, W., Motter, R., Nichols, N. F., Power, M., Robertson, D. W., Schenk, D., Schoor, M., Shopp, G. M., Shuck, M. E., Sinha, S., Svensson, K. A., Tatsuno, G., Tintrup, H., Wijsman, J., Wright, S. and McConlogue, L. (2001) BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: implication for Alzheimer's disease therapeutics. Hum. Mol. Genet. 10, 1317-1324.
44. Farzan, M., Schnitzler, C. E., Vasilieva, N., Leung, D. and Choe, H. (2000) BACE2, a beta-secretase homolog, cleaves at the beta site and within the amyloid-beta region of the amyloid-beta precursor protein. Proc. Natl. Acad. Sci. USA 97, 9712-9717.
45. Bennett, B. D., Babu-Khan, S., Loeloff, R., Loui, J. C., Curran, E., Citron, M. and Vassar, R. (2000) Expression analysis of BACE2 in brain and peripheral tissues. J. Biol. Chem. 275, 20647-20651.
46. Huse, J. T., Liu, K., Pijak, D. S., Carlin, D., Lee, V. M. and Doms, R. W. (2002) Beta-secretase processing in the trans-Golgi network preferentially generates truncated amyloid species that accumulate in Alzheimer's disease brain. J. Biol. Chem. 277, 16278-16284.
47. Holsinger, R. M., McLean, C. A., Beyreuther, K., Masters, C. L. and Evin, G. (2002) Increased expression of the amyloid precursor beta-secretase in Alzheimer's disease. Ann. Neurol. 51, 783-786.
48. Fukumoto, H., Cheung, B. S., Hyman, B. T. and Irizarry, M. C. (2002) Beta-secretase protein and activity are increased in the neocortex in Alzheimer disease. Arch. Neurol. 59, 1381-1389.
49. Basi, G., Frigon, N., Barbour, R., Doan, T., Gordon, G., McConlogue L., Sinha, S. and Zeller, M. (2003) Antagonistic effects of β-site amyloid precursor protein-cleaving enzymes 1 and 2 on β-amyloid peptide production in cells. J. Biol. Chem. 278, 31512-31520.
50. Kao S-C., Krichevsky, A. M., Kosik, K. S. and Tsai L-H. (2004) BACE1 suppression by RNA interference in primary cortical neurons. J. Biol. Chem. 279, 1942-1949.
51. Ohno, M., Sametsky, E. A., Younkin, L. H., Oakley, H., Younkin, S. G., Citron, M., Vassar, R. and Disterhoft, J. F. (2004) BACE1 deficiency rescues memory deficits and cholinergic dysfunction in a mouse model of Alzheimer's disease. Neuron 41, 27-33.
52. Kimura, T., Shuto, D., Hamada, Y., Igawa, N., Kasai, S., Liu, P., Hidaka, K., Hamada, T., Hayashi, Y. and Kiso, Y. (2005) Design and synthesis of highly active Alzheimer's β-secretase (BACE) inhibitors, KMI-420 and KMI-429, with enhanced chemical stability. Bioorg. Med. Chem. Lett. 15, 211-215.
53. Asai, M., Hattori, C., Iwata, N., Saido, T. C., Sasagawa, N., Szabò, B., Hashimoto, Y., Maruyama, K., Tanuma, S., Kiso, Y. and Ishiura, S. (2006) The novel β-secretase inhibitor KMI-429 reduces amyloid β peptide production in amyloid precursor protein transgenic and wild-type mice. J. Neurochem. 96, 533-540.
54. De Strooper, B. (2003) Aph-1, Pen-2, and Nicastrin with Presenilin generate an active gamma-Secretase complex. Neuron 38, 9-12.
55. Edbauer, D., Winkler, E., Regula, J. T., Pesold, B., Steiner, H. and Haass, C. (2003) Reconstitution of gamma-secretase activity. Nat. Cell Biol. 5, 486-488.
56. De Strooper, B., Annaert, W., Cupers, P., Craessaerts, K., Mumm, J. S., Schroeter, E. H., Schrijvers, V., Wolfe, M. S., Ray, W. J., Goate, A. and Kopan, R. (1999) A presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain. Nature 398, 518-522.
57. Hadland, B. K., Manley, N. R., Su, D., Longmore, G. D., Moore, C. L., Wolfe, M. S., Schroeter, E. H. and Kopan, R. (2001) γ-secretase inhibitors repress thymocyte development. Proc. Natl. Acad. Sci. USA 98, 7487-7491.
58. Doerfler, P., Shearman, M. S. and Perlmutter, R. M. (2001) Presenilin-dependent γ-secretase activity modulates thymocyte development. Proc. Natl. Acad. Sci. USA 98, 9312-9317.
59. Weggen, S., Eriksen, J. L. Das, P., Sagi, S. A., Wang, R., Pietrzik, C. U., Findlay, K. A., Smith, T. E., Murphy, M. P., Bulter, T., Kang, D. E., Marguez-Sterling, N., Golde, T. E. and Koo, E. H. (2001) A subset of NSAIDs lower amyloidogenic Abeta42 independently of cyclooxygenase activity. Nature 414, 212-216.
60. Weggen, S., Eriksen, J. L., Sagi, S. A., Pietrzik, C. U., Ozols, V. Fauq, A., Golde, T. E. and Koo, E. H. (2003) Evidence that nonsteroidal anti-inflammatory drugs decrease amyloid beta 42 production by direct modulation of gamma-secretase activity. J. Biol. Chem. 278, 31831-31837.
61. Désiré, L., Bourdin, J., Loiseau, N., Peillon, H., Picard, V., De Oliveila, C., Bachelot, F., Leblond, B., Taverne, T., Beausoleil, E., Lacombe, S., Drouin, D. and Schweighoffer, F. (2005) Rac1 inhibition targets amyloid precursor protein processing by γ-secretase and decreases Aβ production in vitro and in vivo. J. Biol. Chem. 280, 37516-37525.
62. Pakaski, M. and Kasa, P. (2003) Role of acetylcholinesterase inhibitors in the metabolism of amyloid precursor protein. Curr. Drug. Targets CNS Neurol. Disord. 2, 163-171.
63. Hock, C., Maddalena, A., Raschig, A., Muller-Spahn, F., Eschweiler, G., Hager, K., Heuser, I., Hampel, H., Muller-Thomsen, T., Oertel, W., Wienrich, M., Signorell, A., Gonzalez- Agosti, C. and Nitsch, R. M. (2003) Treatment with the selective muscarinic m1 agonist talsaclidine decreases cerebrospinal fluid levels of A beta 42 in patients with Alzheimer's disease. Amyloid 10, 1-6.
64. Nitsch, R. M., Slack, B. E., Wurtman, R. J. and Growdon, J. H. (1992) Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors. Science 258, 304-307.
65. Farris, W., Mansourian, S., Chang, Y., Lindsley, L., Eckman, E. A., Frosch, M. P., Eckman, C. B., Tanzi, R. E., Selkoe, D. J. and Guenette, S. (2003) 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. USA 100, 4162-4167.
66. Eckman, E.A., Watson, M., Marlow, L., Sambamurti, K. and Eckman, C. B. (2003) Alzheimer's disease β-amyloid peptide is increased in mice deficient in endothelin-converting enzyme. J. Biol. Chem. 278, 2081-2084.
67. Tucker, H. M., Kihiko, M., Caldwell, J. N., Wright, S., Kawarabayashi, T. Price, D., Walker, D., Scheff, S., McGillis, J. P., Rydel, R. F. and Estus, S. (2000) The plasmin system is induced by and degrades amyloid-β aggregates. J. Neurosci. 20, 3937-3946.
68. Melchor, J. P., Pawlak, R. and Strickland, S. (2003) The tissue plasminogen activator-plasminogen proteolytic cascade accelerates amyloid-β (Aβ) degradation and inhibits Aβ-induced neurodegeneration. J. Neurosci. 23, 8867-8871.
69. Iwata, N., Tsubuki, S., Takaki, Y., Shirotani, K., Lu, B., Gerard, N. P., Gerard, C., Hama, E., Lee, H. J. and Saido, T. C. (2001) Metabolic regulation of brain Abeta by neprilysin. Science 292, 1550-1552.
70. Yasojima, K., Akiyama, H., McGeer, E. G. and McGeer, P. L. (2001) Reduced neprilysin in high plaque areas of Alzheimer brain: a possible relationship to deficient degradation of β-amyloid peptide. Neurosci. Lett. 297, 97-100.
71. Yasojima, K., McGeer, E. G. and McGeer, P. L. (2001) Relationship between β amyloid peptide generating molecules and neprilysin in Alzheimer disease and normal brain. Brain Res. 919, 115-121.
72. Iwata, N., Takaki, Y., Fukami, S., Tsubuki, S. and Saido, T. C. (2002) Region-specific reduction of Aβ-degrading endopeptidase, neprilysin, in mouse hippocampus upon ageing. J. Neurosci. Res. 70, 493-500.
73. Russo, R., Borghi, R., Makesbery, W., Tabaton, M. and Piccini, A. (2005) Neprylisin decreases uniformly in Alzheimer's disease and in normal aging. FEBS Lett. 579, 6027-6030.
74. Maruyama, M., Higuchi, M., Takaki, Y., Matsuba, Y., Tanji, H., Nemoto, M., Tomita, N., Matsui, T., Iwata, N., Mizukami, H., Muramatsu, S., Ozawa, K., Saido, T. C., Arai, H. and Sasaki, H. (2005) Cerebrospinal fluid neprilysin is reduced in prodromal Alzheimer's disease. Ann. Neurol. 57, 832-842.
75. 42-induced increased neprilysin is associated with prevention of amyloid plaque formation in vivo. J. Biol. Chem. 277, 35460-35465.
76. Mohajeri, M. H., Kuehnle, K., Li, H., Poirier, R., Tracy, J. and Nitsch, R. M. (2004) Anti-amyloid activity of neprilysin in plaque-bearing mouse models of Alzheimer's disease. FEBS Lett. 562, 16-21.
77. Saito, T., Iwata, N., Tsubuki, S., Takaki, Y., Takano, J., Huang, S. M., Suemoto, T., Higuchi, M. and Saido, T. C. (2005) Somatostatin regulates brain amyloid β peptide Aβ42 through modulation of proteolytic degradation. Nat. Med. 11, 434-439.
78. Medina, M. G., Ledesma, M. D., Domínguez, J. E., Medina, M., Zafra, D., Alameda, F., Dotti, C. G. and Navarro, P. (2005) Tissue plasminogen activator mediates amyloid-induced neurotoxicity via Erk1/2 activation. EMBO J. 24, 1706-1716.
79. Solomon, B., Koppel, R., Hanan, E. and Katzav, T. (1996) Monoclonal antibodies inhibit in vitro fibrillar aggregation of the Alzheimer beta-amyloid peptide. Proc. Natl. Acad. Sci. USA 93, 452-455.
80. Solomon, B., Koppel, R., Frankel, D. and Hanan-Aharon, E. (1997) Disaggregation of Alzheimer beta-amyloid by site-directed mAb. Proc. Natl. Acad. Sci. USA 94, 4109-4112.
81. Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Liao, Z., Lieberburg, I., Motter, R., Mutter, L., Soriano, F., Shopp, G., Vasquez, N., Vandevert, C., Walker, S., Wogulis, M., Yednock, T., Games, D. and Seubert, P. (1999) Immunization with amyloid-beta attenuates Alzheimer-disease-like pathology in the PDAPP mouse. Nature 400, 173-177.
82. Bard, F., Cannon, C., Barbour, R., Burke, R. L., Games, D., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., Kholodenko, D., Lee, M., Lieberburg, I., Motter, R., Nguyen, M., Soriano, F., Vasquez, N., Weiss, K., Welch, B., Seubert, P., Schenk, D. and Yednock, T. (2000) Peripherally administered antibodies against amyloid beta-peptide enter the central nervous system and reduce pathology in a mouse model of Alzheimer disease. Nat. Med. 6, 916-919.
83. Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C., Hardy, J., Duff, K., Jantzen, P., DiCarlo, G., Wilcock, D., Connor, K., Hatcher, J., Hope, C., Gordon, M. and Arendash, G. W. (2000) A beta peptide vaccination prevents memory loss in an animal model of Alzheimer's disease. Nature 408, 982-985.
84. DeMattos, R. B., Bales, K. R., Cummins, D. J., Dodart, J. C., Paul, S. M. and Holtzman, D. M. (2001) Peripheral anti-A beta antibody alters CNS and plasma A beta clearance and decreases brain A beta burden in a mouse model of Alzheimer's disease. Proc. Natl. Acad. Sci. USA 98, 8850-8855.
85. DeMattos, R. B., Bales, K. R., Cummins, D. J., Paul, S. M. and Holtzman, D. M. (2002) Brain to plasma amyloid-beta efflux: a measure of brain amyloid burden in a mouse model of Alzheimer's disease. Science 295, 2264-2267.
86. Dodart, J. C., Bales, K. R., Gannon, K. S., Greene, S. J., DeMattos, R. B., Mathis, C., DeLong, C. A., Wu, S., Wu, X., Holtzman, D. M. and Paul, S. M. (2002) Immunization reverses memory deficits without reducing brain Abeta burden in Alzheimer's disease model. Nat. Neurosci. 5, 452-457.
87. McLaurin, J., Cecal, R., Kierstead, M. E., Tian, X., Phinney, A. L., Manea, M., French, J. E., Lambermon, M. H., Darabie, A. A., Brown, M. E., Janus, C., Chishti, M. A., Horne, P., Westaway, D., Fraser, P. E., Mount, H. T., Pizybylski, M. and St. George-Hyslop, P. (2002) Therapeutically effective antibodies against amyloid-beta peptide target amyloid-beta residues 4-10 and inhibit cytotoxicity and fibrillogenesis. Nat. Med. 8, 1263-1269.
88. Orgogozo, J. M., Gilman, S., Dartigues, J. F., Laurent, B., Puel, M., Kirby, L. C., Jouanny, P., Dubois, B., Eisner, L., Flitman, S., Michel, B. F., Boada, M., Frank, A. and Hock, C. (2003) Subacute meningoencephalitis in a subset of patients with AD after Aβ immunization. Neurology 61, 46-54.
89. Gilman, S., Koller, M., Black, R. S., Jenkins, L., Griffith, S. G., Fox, N. C. et al. (2005) Clinical effects of Aβ immunization (AN1792) in patients with AD in an interrupted trial. Neurology 64, 1553-1562.
90. Fox, N. C., Black, R. S., Gilman, S., Rossor, M. N., Griffith, S. G., Jenkins, L. and Koller, M. (2005) Effects of Aβ immunization (AN1792) on MRI measures of cerebral volume in Alzheimer disease. Neurology 64, 1563-72.
91. Nicoll, J. A., Wilkinson, D., Homes, C., Steart, P., Markham, H. and Weller, R. O. (2003) Neuropathology of human Alzheimer disease after immunization with amyloid-beta peptide: a case report. Nat. Med. 9, 448-452.
92. Ferrer, I., Boada Rovira, M., Sanchez Guerra, M. L., Rey, M. J. and Gosta-Jussa, F. (2004) Neuropathology and pathogenesis of encephalitis following amyloid-beta immunization in Alzheimer's disease. Brain Pathol. 14, 11-20.
93. Schenk, D., Hagen, M. and Seubert, P. (2004) Current progress in beta-amyloid immunotherapy. Curr. Opin. Immunol. 16, 599-606.
94. Naiki, H., Higuchi, K., Nakakuki, K. and Takeda, T. (1991) Kinetic analysis of amyloid fibril polymerization in vitro. Lab. Invest. 65, 104-110.
95. Lorenzo, A. and Yankner, B. A. (1994) Beta-amyloid neurotoxicity requires fibril formation and is inhibited by congo red. Proc. Natl. Acad. Sci. USA 91, 12243-12247.
96. Podlisny, M. B., Walsh, D. M., Amarante, P., Ostaszewski, B. L., Stimson, E. R., Maggio, J. E., Teplow, D. B. and Selkoe, D. J. (1998) Oligomerization of endogenous and synthetic amyloid beta-protein at nanomolar levels in cell culture and stabilization of monomer by Congo red. Biochemistry 37, 3602-3611.
97. Bush, A. I., Pettingell, W. H., Multhaup, G., d Paradis, M., Vonsattel, J. P., Gusella, J. F., Beyreuther, K., Masters, C. L. and Tanzi, R. E. (1994) Rapid induction of Alzheimer A beta amyloid formation by zinc. Science 265, 1464-1467.
98. Atwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M., Romano, D. M., Hartshom, M. A., Tanzi, R. E. and Bush, A. I. (1998) Dramatic aggregation of Alzheimer abeta by Cu(II) is induced by conditions representing physiological acidosis. J. Biol. Chem. 273, 12817-12826.
99. Cherny, R. A., Atwood, C. S., Xilinas, M. E., Gray, D. N., Jones, W. D., McLean, C. A., Barnham, K. J., Volitakis, I., Fraser, F. W., Kim, Y., Huang, X., Goldstein, L. E., Moir, R. D., Lim, J. T., Beyreuther, K., Tanzi, R. E., Masters, C. L. and Bush, A. I. (2001) Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer's disease transgenic mice. Neuron 30, 665-676.
100. Ritchie, C. W., Bush, A. I., Mackinnon, A., Macfarlane, S., Mastwyk, M., MacGregor, L., Kiers, L., Cherny, R., Li, Q. X., Tammer, A., Carrington, D., Mavros, C., Volitakis, I., Xilinas, M., Ames, D., Davis, S., Beyreuther, K., Tanzi, R. E. and Masters, C. L. (2003) Metal-protein attenuation with iodochlorhydroxyquin (clioquinol) targeting Abeta amyloid deposition and toxicity in Alzheimer disease: a pilot phase 2 clinical trial. Arch. Neurol. 60, 1685-1691.
101. Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H. and Yamada, M. (2003) Potent anti-amyloidogenic and fibril-destabilizing effects of polyphenols in vitro: implications for the prevention and therapeutics of Alzheimer's disease. J. Neurochem. 87, 172-181.
102. Spencer, C. M., Cai, Y., Martin, R., Gaffney, S. H., Goulding, P. N., Magnolato, D., Lilley, T. H. and Haslam, E. (1988) Polyphenol complexation-some thoughts and observations. Phytochemistry 27, 2397-2409.
103. Haslam, E., Lilley, T. H., Cai, Y., Martin, R. and Magnolato, D. (1989) Traditional herbal medicines-the role of polyphenols. Planta Med. 55, 1-8.
104. Ono, K., Hasegawa, K., Naiki, H. and Yamada, M. (2004) Anti-amyloidogenic activity of tannic acid and its activity to destabilize Alzheimer's beta-amyloid fibrils in vitro. Biochim. Biophys. Acta 1690, 193-202.
105. Ono, K., Hasegawa, K., Yoshiike, Y., Takashima, A., Yamada, M. and Naiki, H. (2002) Nordihydroguaiaretic acid potently breaks down pre-formed Alzheimer's beta-amyloid fibrils in vitro. J. Neurochem. 81, 434-440.
106. Ono, K., Hasegawa, K., Naiki, H. and Yamada, M. (2004) Curcumin has potent anti-amyloidogenic effects for Alzheimer's beta-amyloid fibrils in vitro. J. Neurosci. Res. 75, 742-750.
107. Kim, D. S., Park, S. Y. and Kim, J. K. (2001) Curcuminoids from Curcuma longa, L. (Zingiberaceae) that protect PC12 rat pheochromocytoma and normal human umbilical vein endothelial cells from betaA (1-42) insult. Neurosci. Lett. 303, 57-61.
108. Goodman, Y., Steiner, M. R., Steiner, S. M. and Mattson, M. P. (1994) Nordihydroguaiaretic acid protects hippocampal neurons against amyloid beta-peptide toxicity, and attenuates free radical and calcium accumulation. Brain Res. 654, 171-176.
109. Lim, G. P., Chu, T., Yang, F., Beech, W., Frautschy, S. A. and Cole, G. M. (2001) The curry spice curcumin reduces oxidative damage and amyloid pathology in an Alzheimer transgenic mouse. J. Neurosci. 21, 8370-8377.
110. Yang, F., Lim, G. P., Begum, A. N., Ubeda, O. J., Simmons, M. R., Ambegaokar, S. S., Chen, P. P., Kayed, R., Glabe, C. G., Frautzchy, S. A. and Cole, G. M. (2005) Curcumin inhibits formation of amyloid β oligomers and fibrils, binds plaques, and reduces amyloid in vivo. J. Biol. Chem. 280, 5892-5901.
111. Lerner, A., Koss, E., Debanne, S., Rowland, D., Smyth, K. and Friedland, R. (1997) Smoking and oestrogen-replacement therapy as protective factors for Alzheimer's disease. Lancet 349, 403-404.
112. Ulrich, J., Johannson-Locher, G., Seiler, W. O. and Stähelin, H. B. (1997) Does smoking protect from Alzheimer's disease? Alzheimer-type changes in 301 unselected brains from patients with known smoking history. Acta. Neuropathol. 94, 450-454.
113. Kihara, T., Shimohama, S., Sawada, H., Kimura, J., Kume, T., Kochiyama, H., Maeda, T. and Akaike, A. (1997) Nicotinic receptor stimulation protects neurons against β-amyloid toxicity. Ann. Neurol. 42, 159-163.
114. Zamani, M. R., Allen, Y. S., Owen, G. P. and Gray, J. A. (1997) Nicotine modulates the neuro toxic effect of β-amyloid protein (25-35) in hippocampal cultures. Neuroreport 8, 513-517.
115. Salomon, A. R., Marcinowski, K. J., Friedland, R. P. and Zagorski, M. G. (1996) Nicotine inhibits amyloid formation by the β-peptides. Biochemistry 35, 13568-13578.
116. Ono, K., Hasegawa, K., Yamada, M. and Naiki, H. (2002) Nicotine breaks down preformed Alzheimer's beta-amyloid fibrils in vitro. Biol. Psychiatry 52, 880-886.
117. Nordberg, A., Hellstrom-Lindahl, E., Lee, M., Johnson, M., Mousavi, M., Hall, R., Perry, E., Bednar, I. and Court, J. (2002) Chronic nicotine treatment reduces beta-amyloidosis in the brain of a mouse model of Alzheimer's disease (AP-Psw). J. Neurochem. 81, 655-658.
118. Tomiyama, T., Asano, S., Suwa, Y., Morita, T., Kataoka, K., Mori, H. and Endo, N. (1994) Rifampicin prevents the aggregation and neurotoxicity of amyloid beta protein in vitro. Biochem. Biophys. Res. Commun. 204, 76-83.
119. Tomiyama, T., Shoji, A., Kataoka, K., Suwa, Y., Asano, S., Kaneko, H., Mori, H. and Endo, N. (1996) Inhibition of amyloid beta protein aggregation and neurotoxicity by rifampicin. Its possible function as a hydroxyl radical scavenger. J. Biol. Chem. 271, 6839-6844.
120. Naiki, H., Hasegawa, K., Yamaguchi, I., Nakamura, H., Gejyo, F. and Nakakuki, K. (1998) Apolipoprotein E and antioxidants have different mechanisms of inhibiting Alzheimer's beta-amyloid fibril formation in vitro. Biochemistry 37, 17882-17889.
121. Forloni, G., Colombo, L., Girola, L., Tagliavini, F. and Salmona, M. (2001) Anti-amyloidogenic activity of tetracyclines: studies in vitro. FEBS Lett. 487, 404-407.
122. Loeb, M. B., Molloy, D. W., Smieja, M., Standish, T., Goldsmith, C. H., Mahony, J., Smith, S., Borrie, M., Decoteau, E., Davidson, W., McDougall, A., Gnarpe, J., O'Donnell, M. and Chernesky, M. (2004) A randomized, controlled trial of doxycycline and rifampin for patients with Alzheimer's disease. J. Am. Geriatr. Soc. 52, 381-387.
123. Behl, C., Davis, J., Cole, G. M. and Schubert, D. (1992) Vitamin E protects nerve cells from amyloid beta protein toxicity. Biochem. Biophys. Res. Commun. 186, 944-950.
124. Zhou, Y., Gopalakrishnan, V. and Richardson, J. S. (1996) Actions of neurotoxic beta-amyloid on calcium homeostasis and viability of PC12 cells are blocked by antioxidants but not by calcium channel antagonists. J. Neurochem. 67, 1419-1425.
125. Subramaniam, R., Koppal, T., Green, M., Yatin, S., Jordan, B., Drake, J. and Butterfield, D. A. (1998) The free radical antioxidant vitamin E protects cortical synaptosomal membranes from amyloid beta-peptide(25-35) toxicity but not from hydroxynonenal toxicity: relevance to the free radical hypothesis of Alzheimer's disease. Neurochem. Res. 23, 1403-1410.
126. Pereira, C., Santos, M. S. and Oliveira, C. (1999) Involvement of oxidative stress on the impairment of energy metabolism induced by A beta peptides on PC12 cells: protection by antioxidants. Neurobiol. Dis. 6, 209-219.
127. Yatin, S. M., Yatin, M., Aulick, T., Ain, K. B. and Butterfield, D. A. (1999) Alzheimer's amyloid beta-peptide associated free radicals increase rat embryonic neuronal polyamine uptake and ornithine decarboxylase activity: protective effect of vitamin, E. Neurosci. Lett. 263, 17-20.
128. Behl, C., Davis, J. B., Lesley, R. and Schubert, D. (1994) Hydrogen peroxide mediates amyloid beta protein toxicity. Cell 77, 817-827.
129. Yallampalli, S., Micci, M. A. and Taglialatela, G. (1998) Ascorbic acid prevents beta-amyloid-induced intracellular calcium increase and cell death in PC12 cells. Neurosci. Lett. 251, 105-108.
130. Jama, J. W., Launer, L. J., Witteman, J. C., den Breeijen, J. H., Breteler, M. M., Grobbee, D. E. and Hofman, A. (1996) Dietary antioxidants and cognitive function in a population-based sample of older persons. The Rotterdam Study. Am. J. Epidemiol. 144, 275-280.
131. Perrig, W. J., Perrig, P. and Stahelin, H., B. (1997) The relation between antioxidants and memory performance in the old and very old. J. Am. Geriatr. Soc. 45, 718-724.
132. Zaman, Z., Roche, S., Fielden, P., Frost, P. G., Niriella, D. C. and Cayley, A. C. (1992) Plasma concentrations of vitamins A and E and carotenoids in Alzheimer's disease. Age Ageing 21, 91-94.
133. Jimenez-Jimenez, F. J., de Bustos, F., Molina, J. A., Benito-Leon, J., Tallon-Barranco, A., Gasalla T, Orti-Pareja, M., Guillamon, F., Rubio, J. C., Arenas, J. and Enriquez-de-Salamanca, R. (1997) Cerebrospinal fluid levels of alpha-tocopherol (vitamin E) in Alzheimer's disease. J. Neural. Transm. 104, 703-710.
134. Riviere, S., Birlouez-Aragon I, Nourhashemi, F. and Vellas, B. (1998) Low plasma vitamin C in Alzheimer patients despite an adequate diet. Int. J. Geriatr. Psychiatry 13, 749-754.
135. Jimenez-Jimenez, F. J., Molina, J. A., de Bustos, F., Orti-Pareja, M., Benito-Leon, J., Tallon-Barranco, A., Gasalla, T., Porta, J. and Arenas, J. (1999) Serum levels of beta-carotene, alpha-carotene and vitamin A in patients with Alzheimer's disease. Eur. J. Neurol. 6, 495-497.
136. Sano, M., Ernesto, C., Thomas, R. G., Klauber, M. R., Schafer, K., Grundman, M., Woodbury, P., Cotman, C. W., Pfeiffer, E., Schneider, L. S. and Thal, L. J. (1997) A controlled trial of selegiline, alpha-tocopherol, or both as treatment for Alzheimer's disease. The Alzheimer's Disease Cooperative Study. N. Engl. J. Med. 336, 1216-1222.
137. Morris, M. C., Beckett, L. A., Scherr, P. A., Hebert, L. E., Bennett, D. A., Field, T. S. and Evans, D. A. (1998) Vitamin E and vitamin C supplement use and risk of incident Alzheimer disease. Alzheimer Dis. Assoc. Disord. 12, 121-126.
138. Paleologos, M., Cumming, R. G. and Lazarus, R. (1998) Cohort study of vitamin C intake and cognitive impairment. Am. J. Epidemiol. 148, 45-50.
139. Engelhart, M. J., Ruitenberg, A., Swieten, J. C., Witteman, J. C. M., Hofman, A. and Breteler, M. B. (2000) Dietary antioxidants and the risk of dementia. The Rotterdam study. Neurobiol. Aging 21, 203S.
140. Morris, M. C., Evans, D. A., Bienias, J. L., Tangney, C. C. and Wilson, R. S. (2002) Vitamin E and cognitive decline in older persons. Arch. Neurol. 59, 1125-1132.
141. Ono, K., Yoshiike, Y., Takashima, A., Hasegawa, K., Naiki, H. and Yamada, M. (2004) Vitamin A exhibits potent antiamyloidogenic and fibril-destabilizing effects in vitro. Exp. Neurol. 189, 380-392.
142. Reiter, R. J. (1992) The ageing pineal gland and its physiological consequences. Bioessays 14, 169-175.
143. Souetre, E., Salvati, E., Krebs, B., Belugou, J. L. and Darcourt, G. (1989) Abnormal melatonin response to 5-methoxy-psoralen in dementia. Am. J. Psychiatry 146, 1037-1040.
144. Mishima, K., Okawa, M., Hishikawa, Y., Hozumi, S., Hori, H. and Takahashi, K. (1994) Morning bright light therapy for sleep and behavior disorders in elderly patients with dementia. Acta. Psychiatr. Scand. 89, 1-7.
145. Liu, R. Y., Zhou, J. N., van Heerikhuize, J., Hofman, M. A. and Swaab, D. F. (1999) Decreased melatonin levels in post-mortem cerebrospinal fluid in relation to aging, Alzheimer's disease, and apolipoprotein E-epsilon4/4 genotype. J. Clin. Endocrinol. Metab. 84, 323-327.
146. Pappolla, M., Bozner, P., Soto, C., Shao, H., Robakis, N. K., Zagorski, M., Frangione, B. and Ghiso, J. (1998) Inhibition of Alzheimer beta-fibrillogenesis by melatonin. J. Biol. Chem. 273, 7185-7188.
147. Poeggeler, B., Miravalle, L., Zagorski, M. G., Wisniewski, T., Chyan, Y. J., Zhang, Y., Shao, H., Bryant-Thomas, T., Vidal, R., Frangione, B., Ghiso, J. and Pappolla, M. A. (2001) Melatonin reverses the profibrillogenic activity of apolipoprotein E4 on the Alzheimer amyloid Abeta peptide. Biochemistry 40, 14995-15001.
148. Matsubara, E., Bryant-Thomas, T., Pacheco Quinto, J., Henry, T. L., Poeggeler, B., Herbert, D., Cruz-Sanchez, F., Chyan, Y. J., Smith, M. A., Perry, G., Shoji, M., Abe, K., Leone, A., Grundke-Ikbal, I., Wilson, G. L., Ghiso, J., Williams, C., Refolo, L. M., Pappolla, M. A., Chain, D. G. and Neria, E. (2003) Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease. J. Neurochem. 85, 1101-1108.
149. Pike, C. J., Burdick, D., Walencewicz, A. J., Glabe, C. G. and Cotman, C. W. (1993) Neurodegeneration induced by beta-amyloid peptides in vitro: the role of peptide assembly state. J. Neurosci. 13, 1676-1687.
150. Yankner, B. A. (1996) Mechanisms of neuronal degeneration in Alzheimer's disease. Neuron 16, 921-932.
151. Soto, C., Kindy, M. S., Baumann, M. and Frangione, B. (1996) Inhibition of Alzheimer's amyloidosis by peptides that prevent beta-sheet conformation. Biochem. Biophys. Res. Commun. 226, 672-680.
152. Soto, C., Sigurdsson, E. M., Morelli, L., Kumar, R. A., Castano, E. M. and Frangione, B. (1998) Beta-sheet breaker peptides inhibit fibrillogenesis in a rat brain model of amyloidosis: implications for Alzheimer's therapy. Nat. Med. 4, 822-826.
153. Permanne, B., Adessi, C., Saborio, G. P., Fraga, S., Frossard, M. J., Van Dorpe, J., Dewachter, I., Banks, W. A., Van Leuven, F. and Soto, C. (2002) Reduction of amyloid load and cerebral damage in a transgenic mouse model of Alzheimer's disease by treatment with a beta-sheet breaker peptide. FASEB J. 16, 860-862.
154. Chacon, M. A., Barria, M. I., Soto, C. and Inestrosa, N. C. (2004) Beta-sheet breaker peptide prevents Abeta-induced spatial memory impairments with partial reduction of amyloid deposits. Mol. Psychiatry 9, 953-961.
155. Snow, A. D., Sekiguchi, R. T., Nochlin, D., Kalaria, R. N. and Kimata, K. (1994) Heparan sulfate proteoglycan in diffuse plaques of hippocampus but not of cerebellum in Alzheimer's disease brain. Am. J. Pathol. 144, 337-347.
156. Fraser, P. E., Nguyen, J. T., Chin, D. T. and Kirschner, D. A. (1992) Effects of sulfate ions on Alzheimer beta/A4 peptide assemblies: implications for amyloid fibril-proteoglycan interactions. J. Neurochem. 59, 1531-1540.
157. Kisilevsky, R., Lemieux, L. J., Fraser, P. E., Kong, X., Hultin, P. G. and Szarek, W. A. (1995) Arresting amyloidosis in vivo using small-molecule anionic sulphonates or sulphates: implications for Alzheimer's disease. Nat. Med. 1, 143-148.
158. Bergamaschini, L., Rossi, E., Storini, C., Pizzimenti, S., Distaso, M., Perego, C., De Luigi, A., Vergani, C. and De Simoni, M. G. (2004) Peripheral treatment with enoxaparin, low molecular weight heparin, reduces plaques and b-amyloid accumulation in a mouse model of Alzheimer's disease. J. Neurosci. 24, 4181-4186.