• 1
    Selkoe, D.J. (2001) Alzheimer's disease: genes, proteins, and therapy. Physiol. Rev. 81, 741766.
  • 2
    Gorman, P.M. & Chakrabartty, A. (2001) Alzheimer beta- amyloid peptides: structures of amyloid fibrils and alternate aggregation products. Biopolymers 60, 381394.
  • 3
    Tanzi, R.E., Gusella, J.F., Watkins, P.C., Bruns, G.A., St George-Hyslop, P., Van Keuren, M.L., Patterson, D., Pagan, S., Kurnit, D.M. & Neve, R.L. (1987) Amyloid beta protein gene: cDNA, mRNA distribution, and genetic linkage near the Alzheimer locus. Science 235, 880884.
  • 4
    Goldgaber, D., Lerman, M.I., McBride, O.W., Saffiotti, U. & Gajdusek, D.C. (1987) Characterization and chromosomal localization of a cDNA encoding brain amyloid of Alzheimer's disease. Science 235, 877880.
  • 5
    Busciglio, J., Gabuzda, D.H., Matsudaira, P. & Yankner, B.A. (1993) Generation of beta-amyloid in the secretory pathway in neuronal and nonneuronal cells. Proc. Natl Acad. Sci. USA 90, 20922096.
  • 6
    Haass, C., Schlossmacher, M.G., Hung, A.Y., Vigo-Pelfrey, C., Mellon, A., Ostaszewski, B.L., Lieberburg, I., Koo, E.H., Schenk, D., Teplow, D.B. & Selkoe, D.J. (1992) Amyloid β-protein is produced by cultured cells during normal metabolism. Nature 359, 322325.
  • 7
    Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Sinha, S., Schlossmacher, M.G., Whaley, J., Swindlehurst, C., McCormack, R., Wolfert, R., Selkoe, D.J., Lieberburg, I. & Schenk, D. (1992) Isolation and quantification of soluble Alzheimer's β-peptide from biological fluids. Nature 359, 325327.
  • 8
    Shoji, M., Golde, T.E., Ghiso, J., Cheung, T.T., Estus, S., Shaffer, L.M., Cai, X.D., McKay, D.M., Tintner, R., Frangione, B. & Younkin, S.G. (1992) Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258, 126129.
  • 9
    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. (1991) Segregation of a missense mutation in the amyloid precursor protein gene with familial Alzheimer's disease. Nature 349, 704706.
  • 10
    Murrell, J., Farlow, M., Ghetti, B. & Benson, M.D. (1991) A mutation in the amyloid precursor protein associated with hereditary Alzheimer's disease. Science 254, 9799.
  • 11
    Suzuki, N., Iwatsubo, T., Odaka, A., Ishibashi, Y., Kitada, C. & Ihara, Y. (1994) High tissue content of soluble beta 1–40 is linked to cerebral amyloid angiopathy. Am. J. Pathol. 145, 452460.
  • 12
    Masliah, E., Sisk, A., Mallory, M., Mucke, L., Schenk, D. & Games, D.(1996) Comparison of neurodegenerative pathology in transgenic mice overexpressing V717F beta-amyloid precursor protein and Alzheimer's disease. J. Neurosci. 16, 57955811.
  • 13
    Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F. & Cole, G. (1996) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Science 274, 99102.
  • 14
    Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.H., Mistl, C., Rothacher, S., Ledermann, B., Burki, K., Frey, P., Paganetti, P.A., Waridel, C., Calhoun, M.E., Jucker, M., Probst, A., Staufenbiel, M. & Sommer, B. (1997) Correlative memory deficits, Abeta elevation, and amyloid plaques in transgenic mice. Proc. Natl Acad. Sci. USA 94, 1328713292.
  • 15
    Tokuda, T., Fukushima, T., Ikeda, S., Sekijima, Y., Shoji, S., Yanagisawa, N. & Tamoaka, A. (1997) Plasma levels of amyloid beta proteins Abeta1-40 and Abeta1-42(43) are elevated in Down's syndrome. Ann. Neurol. 41, 271273.
  • 16
    Yamaguchi, H. , Nakazato, Y., Shoji, M., Takatama, M. & Hirai, S. (1991) Ultrastructure of diffuse plaques in senile dementia of the Alzheimer type: comparison with primitive plaques. Acta Neuropathol. 82, 1320.
  • 17
    Tagliavini, F., Giaccone, G., Frangione, B. & Bugiani, O. (1988) Preamyloid deposits in the cerebral cortex of patients with Alzheimer's disease and nondemented individuals. Neurosci. Lett. 93, 191196.
  • 18
    Yamaguchi, H., Hirai, S., Morimatsu, M., Shoji, M. & Ihara, Y. (1988) A variety of cerebral amyloid deposits in the brains of the Alzheimer-type dementia demonstrated by beta protein immunostaining. Acta Neuropathol. (Berl.) 76, 541549.
  • 19
    Joachim, C.L., Morris, J.H. & Selkoe, D.J. (1989) Diffuse senile plaques occur commonly in the cerebellum in Alzheimer's disease. Am. J. Pathol. 135, 309319.
  • 20
    Yamaguchi, H., Nakazato, Y., Hirai, S., Shoji, M. & Harigaya, Y. (1989) Electron micrograph of diffuse plaques. Initial stage of senile plaque formation in the Alzheimer brain. Am. J. Pathol. 135, 593597.
  • 21
    Lemere, C.A., Blustzjan, J.K., Yamaguchi, H., Wisniewski, T., Saido, T.C. & 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, 1632.
  • 22
    Hardy, J. (1997) Amyloid, the presenilins and Alzheimer's disease. Trends Neurosci. 20, 154159.
  • 23
    Hasegawa, K., Yamaguchi, I., Omata, S., Gejyo, F. & Naiki, H. (1999) Interaction between A beta (1–42) and A beta (1–40) in Alzheimer's beta-amyloid fibril formation in vitro. Biochemistry 38, 1551415521.
  • 24
    Walsh, D.M., Klyubin, I., Fadeeva, J.V., Cullen, W.K., Anwyl, R., Wolfe, M.S., Rowan, M.J. & Selkoe, D.J. (2002) Naturally secreted oligomers of amyloid beta protein potently inhibit hippocampal long-term potentiation in vivo. Nature 416, 535539.
  • 25
    Huang, T.H., Yang, D.S., Plaskos, N.P., Go, S., Yip, C.M., Fraser, P.E. & Chakrabartty, A. (2000) Structural studies of soluble oligomers of the Alzheimer beta-amyloid peptide. J. Mol. Biol. 297, 7387.
  • 26
    Stine, W.B. Jr, Snyder, S.W., Ladror, U.S., Wade, W.S., Miller, M.F., Perun, T.J., Holzman, T.F. & Krafft, G.A. (1996) The nanometer-scale structure of amyloid-beta visualized by atomic force microscopy. J. Protein Chem. 15, 193203.
  • 27
    Harper, J.D. & Lansbury, P.T. (1997) Models of amyloid seeding in Alzheimer's disease and scrapie: mechanistic truths and physiological consequences of the time-dependent solubility of amyloid proteins. Annu. Rev. Biochem. 66, 385407.
  • 28
    Walsh, D.M., Lomakin, A., Benedek, G.B., Condron, M.M. & Teplow, D.B. (1997) Amyloid beta-protein fibrillogenesis. Detection of a protofibrillar intermediate. J. Biol. Chem. 272, 2236422372.
  • 29
    Walsh, D.M., Hartley, D.M., Kusumoto, Y., Fezoui, Y., Condron, M.M., Lomakin, A., Benedek, G.B., Selkoe, D.J. & Teplow, D.B. (1999) Amyloid beta-protein fibrillogenesis. Structure and biological activity of protofibrillar intermediates. J. Biol. Chem. 274, 2594525952.
  • 30
    Edelhoch, H. (1967) Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 6, 19481954.
  • 31
    Hudson, E.N. & Weber, G. (1973) Synthesis and characterization of two fluorescent sulfhydryl reagents. Biochemistry 12, 41544161.
  • 32
    Huang, T.H., Fraser, P.E. & Chakrabartty, A. (1997) Fibrillogenesis of Alzheimer beta-amyloid peptides studied by fluorescence energy transfer. J. Mol. Biol. 269, 214224.
  • 33
    Krebs, M.R., Wilkins, D.K., Chung, E.W., Pitkeathly, M.C., Chamberlain, A.K., Zurdo, J., Robinson. C.V. & Dobson, C.M. (2000) Formation and seeding of amyloid fibrils from wild-type hen lysozyme and a peptide fragment from the beta-domain. J. Mol. Biol. 300, 541549.
  • 34
    Huang, T.H., Yang, D.S., Fraser, P.E. & Chakrabartty, A. (2000) Alternate aggregation pathways of the Alzheimer beta-amyloid peptide: an in vitro model of diffuse amyloid. J. Biol. Chem. 275, 3643636440.
  • 35
    Suzuki, N., Cheung, T.T., Cai, X.D., Odaka, A., Otvos, L., Eckman, C., Golde, T.E. & Younkin, S.G. (1994) An increased percentage of long amyloid beta protein secreted by familial amyloid beta protein precursor (beta APP717) mutants. Science 264, 13361340.