The Swedish mutation causes early-onset Alzheimer's disease by β-secretase cleavage within the secretory pathway

Selkoe, D.J. Cell biology of the amyloid β-protein precursor and the mechanism of Alzheimer's disease. Annu. Rev. Cell Biol. 10, 373–403 (1994).

Kang, J.H. et al. The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor. Nature 325, 733–736 (1987).

Haass, C. & Selkoe, D.J. Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide. Cell 75, 1039–1042 (1993).

Esch, F.S. et al. Cleavage of amyloid β-peptide during constitutive processing of its precursor. Science 248, 1122–1124 (1990).

Sisodia, S.S., Koo, E.H., Beyreuther, K., Unterbeck, A. & Price, D.L. Evidence that β-amyloid protein in Alzheimer's disease is not derived by normal processing. Science 248, 492–495 (1990).

Weidemann, A. et al. Identification, biogenesis and localization of precursors of Alzheimer's disease A4 amyloid protein. Cell 57, 115–126 (1989).

Haass, C. et al. Amyloid β-peptide is produced by cultured Cells during normal metabolism. Nature 359, 322–325 (1992).

Shoji, M. et al. Production of the Alzheimer amyloid β protein by normal proteolytic processing. Science 258, 126–129 (1992).

Mullan, M. & Crawford, F. Genetic and molecular advances in Alzheimer's disease. Trends Neurosci. 16, 398–403 (1993).

Citron, M. et al. Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production. Nature 360, 672–674 (1992).

Cai, X., Golde, T. & Younkin, S. Release of excess amyloid βprotein from a mutant amyloid β protein precursor. Science 259, 514–516 (1993).

Felsenstein, K.M., Hunihan, L.W. & Roberts, S. Altered cleavage and secretion of a recombinant β-APP bearing the Swedish familial Alzheimer's disease mutation. Nature Genet. 6, 251–256 (1994).

Suzuki, N. et al. An increased percentage of long amyloid β-protein secreted by familial amyloid β protein precursor (βAPP717) mutants. Science 264, 1336–1340 (1994).

Jarrett, J. & Lansbury, P. Seeding “one-dimensional crystallization” of amyloid: A pathogenic mechanism in Alzheimer's disease and scrapie? Cell 73, 1055–1058 (1993).

Haass, C., Hung, A.Y., Selkoe, D.J. & Teplow, D.B. Mutations associated with a locus for familial Alzheimer's disease result in alternative processing of amyloid β-amyloid protein precursor. J. biol. Chem. 269, 17741–17748 (1994).

Haass, C., Koo, E.H., Capell, A., Teplow, D.B. & Selkoe, D.J. Polarized sorting of β-amyloid precursor protein and its proteolytic products in MDCK cells is regulated by two independent signals. J. Cell Biol. 128, 537–547 (1995).

Kuentzel, S.L., Ali, S.M., Altman, R.A., Greenberg, B.D. & Raub, T.J. The Alzheimer β-amyloid protein precursor/protease nexin-II is cleaved by secretase in a trans-Golgi secretory compartment in human neuroglioma cells. Biochem. J. 295, 367–378 (1993).

Nordstedt, C., Caporaso, G., Thyberg, J., Gandy, S. & Greengard, P. Identification of the Alzheimer β/A4 amyloid precursor protein in clathrin-coated vesicles purified from PC12 cells. J. Biol. Chem. 268, 608–612 (1993).

Haass, C., Koo, E.H., Mellon, A., Hung, A.Y. & Selkoe, D.J. Targeting of cell-surface β-amyloid precursor protein to lysosomes: Alternative processing into amyloid-bearing fragments. Nature 357, 500–503 (1992).

Lai, A., Sisodia, S. & Trowbridge, I.S. Characterization of sorting signals in the β-amyloid precursor protein cytoplasmic domain. J. biol. Chem. 270, 3565–3573 (1995).

Golde, T.E., Estus, S., Younkin, L.H., Selkoe, D.J. & Younkin, S. Processing of the amyloid protein precursor to potentially amyloidogenic carboxyl-terminal derivatives. Science 255, 728–730 (1992).

Haass, C., Hung, A.Y., Schlossmacher, M.G., Teplow, D.B. & Selkoe, D.J. β-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms. J. biol. Chem. 268, 3021–3024 (1993).

Koo, E.H. & Squazzo, S. Evidence that production and release of amyloid β-protein involves the endocytic pathway. J. biol. Chem. 269, 17386–17389 (1994).

Lo, A.C.Y., Haass, C., Wagner, S.L., Teplow, D.B. & Sisodia, S.S. Metabolism of the “Swedish” amyloid precursor protein variant in Madin-Darby canine kidney cells. J. biol. Chem. 269, 30966–30973 (1994).

De Strooper, B. et al. Basolateral secretion of amyloid precursor protein in Madin-Darby canine kidney cells is disturbed by alterations of intracellular pH and by introducing a mutation associated with familial Alzheimer's disease. J. biol. Chem. 270, 4058–4065 (1995).

Knops, J. et al. Cell-type and APP-type specific inhibition of Aβ release by bafilomycin Al, a selective inhibitor of vacuolar ATPases. J. biol. Chem. 270, 2419–2422 (1995).

Kelly, R.B. Microtubules, membrane traffic, and cell organization. Cell 61, 5–7 (1990).

Matlin, K.S. & Simons, K. Reduced temperature prevents transfer of a membrane glycoprotein to the cell surface but does not prevent terminal glycosylation. Cell 34, 233–243 (1983).

Chen, J.W., Murphy, T.L., Willingham, M.C., Pastan, I. & August, T. Identification of two lysosomal membrane glycoproteins. J. Cell Biol. 101, 85–95 (1985).

Citron, M., Teplow, D.B. & Selkoe, D.J. Generation of amyloid βprotein from its precursor is sequence specific. Neuron 14, 661–670 (1995).

Haass, C., Capell, A., Citron, M., Teplow, D. & Selkoe, D.J. The vacuolar H+ ATPase inhibitor bafilomycin Al differentially affects proteolytic processing of mutant and wild-type β-amyloid precursor protein. J. biol. Chem. 270, 6186–6192 (1995).w

Hung, A. et al. Activation of protein kinase C inhibits cellular production amyloid β-protein. J. biol. Chem. 268, 22956–22962 (1993).

Yamazaki, T., Selkoe, D.J. & Koo, E.H. Trafficking of Cell-surface β-amyloid precursor protein: Retrograde and transcytotic transport in cultured neurons. J. Cell Biol. 129, 431–442 (1995).