The Swedish mutation causes early-onset Alzheimer's disease by β-secretase cleavage within the secretory pathway
Abstract
Several missense mutations causing early-onset Alzheimer's disease (AD) have been described in the gene coding for the beta-amyloid precursor protein (beta APP). A double mutation found in a Swedish family is located before the amyloid beta-peptide (A beta) region of beta APP and results in the increased production and secretion of A beta. Here we show that the increased production of A beta results from a cellular mechanism, which differs substantially from that responsible for the production of A beta from wild-type beta APP. In the latter case, A beta generation requires reinternalization and recycling of beta APP. In the case of the Swedish mutation the N-terminal beta-secretase cleavage of A beta occurs in Golgi-derived vesicles, most likely within secretory vesicles. Therefore, this cleavage occurs in the same compartment as the alpha-secretase cleavage, which normally prevents A beta production, explaining the increased A beta generation by a competition between alpha- and beta-secretase.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The Swedish APP FAD mutation enhances BACE-mediated APP cleavage.
“However, the extensively characterized Swedish APP FAD mutation (APPswe, K595N/M596L) resides adjacently to the BACE1 cleavage site, thereby enhancing BACE-mediated APP cleavage [39].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [39]
Cites
The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor
Kang, J., Lemaire, H.-G., Unterbeck, A., Salbaum, J. M., Masters, C. L., Grzeschik, K.-H., Multhaup, G., Beyreuther, K., & Müller-Hill, B. (1987) · Nature · doi:10.1038/325733a0 · Cited by 4,619 · see citing works
Jarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178 · see citing works
Amyloid β-peptide is produced by cultured cells during normal metabolism
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., et al. (1992) · Nature · doi:10.1038/359322a0 · Cited by 1,921 · see citing works
Self-citationCitron, M., Oltersdorf, T., Haass, C., McConlogue, L., Hung, A. Y., Seubert, P., Vigo-Pelfrey, C., Lieberburg, I., & Selkoe, D. J. (1992) · Nature · doi:10.1038/360672a0 · Cited by 1,757 · see citing works
Self-citationSuzuki, N., Cheung, T. T., Cai, X.-D., Odaka, A., Otvos, L., Eckman, C., Golde, T. E., & Younkin, S. G. (1994) · Science · doi:10.1126/science.8191290 · Cited by 1,471 · see citing works
Production of the Alzheimer Amyloid β Protein by Normal Proteolytic Processing
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., et al. (1992) · Science · doi:10.1126/science.1439760 · Cited by 1,447 · see citing works
Cleavage of Amyloid β Peptide During Constitutive Processing of Its Precursor
Esch, F. S., Keim, P. S., Beattie, E. C., Blacher, R. W., Culwell, A. R., Oltersdorf, T., McClure, D., & Ward, P. J. (1990) · Science · doi:10.1126/science.2111583 · Cited by 1,403 · see citing works
Identification, biogenesis, and localization of precursors of Alzheimer's disease A4 amyloid protein
Weidemann, A., König, G., Bunke, D., Fischer, P. Q., Salbaum, J. M., Masters, C. L., & Beyreuther, K. T. (1989) · Cell · doi:10.1016/0092-8674(89)90177-3 · Cited by 1,233 · see citing works
Evidence that production and release of amyloid beta-protein involves the endocytic pathway
Koo, E. H., & Squazzo, S. L. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32449-3 · Cited by 989 · see citing works
Release of Excess Amyloid β Protein from a Mutant Amyloid β Protein Precursor
Cai, X.-D., Golde, T. E., & Younkin, S. G. (1993) · Science · doi:10.1126/science.8424174 · Cited by 913 · see citing works
Haass, C., Koo, E. H., Mellon, A., Hung, A. Y., & Selkoe, D. J. (1992) · Nature · doi:10.1038/357500a0 · Cited by 899 · see citing works
Self-citationEvidence that β-Amyloid Protein in Alzheimer's Disease Is Not Derived by Normal Processing
Sisodia, S. S., Koo, E. H., Beyreuther, K. T., Unterbeck, A., & Price, D. L. (1990) · Science · doi:10.1126/science.1691865 · Cited by 894 · see citing works
Cellular processing of β-amyloid precursor protein and the genesis of amyloid β-peptide
Haass, C., & Selkoe, D. J. (1993) · Cell · doi:10.1016/0092-8674(93)90312-e · Cited by 833 · see citing works
Self-citationCell Biology of the Amyloid beta-Protein Precursor and the Mechanism of Alzheimer's Disease
Selkoe, D. J. (1994) · Annual Review of Cell Biology · doi:10.1146/annurev.cb.10.110194.002105 · Cited by 748 · see citing works
Self-citationProcessing of the Amyloid Protein Precursor to Potentially Amyloidogenic Derivatives
Golde, T. E., Estus, S., Younkin, L. H., Selkoe, D. J., & Younkin, S. G. (1992) · Science · doi:10.1126/science.1738847 · Cited by 737 · see citing works
Self-citationMatlin, K. S., & Simons, K. (1983) · Cell · doi:10.1016/0092-8674(83)90154-x · Cited by 508 · see citing works
Identification of two lysosomal membrane glycoproteins.
Chen, J. W., Murphy, T. L., Willingham, M. C., Pastan, I. H., & August, J. T. (1985) · The Journal of Cell Biology · doi:10.1083/jcb.101.1.85 · Cited by 485 · see citing works
beta-Amyloid peptide and a 3-kDa fragment are derived by distinct cellular mechanisms.
Haass, C., Hung, A. Y., Schlossmacher, M. G., Teplow, D. B., & Selkoe, D. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53650-4 · Cited by 465 · see citing works
Self-citationActivation of protein kinase C inhibits cellular production of the amyloid beta-protein.
Hung, A. Y., Haass, C., Nitsch, R. M., Qiu, W. Q., Citron, M., Wurtman, R. J., Growdon, J. H., & Selkoe, D. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)49409-x · Cited by 399 · see citing works
Self-citationHaass, C., Hung, A. Y., Selkoe, D. J., & Teplow, D. B. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32503-6 · Cited by 315 · see citing works
Self-citationGeneration of amyloid β protein from its precursor is sequence specific
Citron, M., Teplow, D. B., & Selkoe, D. J. (1995) · Neuron · doi:10.1016/0896-6273(95)90323-2 · Cited by 263 · see citing works
Self-citationMicrotubules, membrane traffic, and cell organization
Kelly, R. B. (1990) · Cell · doi:10.1016/0092-8674(90)90206-t · Cited by 228 · see citing works
Nordstedt, C., Caporaso, G. L., Thyberg, J., Gandy, S., & Greengard, P. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)54194-6 · Cited by 208 · see citing works
Yamazaki, T., Selkoe, D. J., & Koo, E. H. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.129.2.431 · Cited by 207 · see citing works
Self-citationCharacterization of Sorting Signals in the β-Amyloid Precursor Protein Cytoplasmic Domain
Lai, A., Sisodia, S. S., & Trowbridge, I. S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.8.3565 · Cited by 197 · see citing works
Genetics and molecular advances in Alzheimer's disease
Mullan, M., & Crawford, F. (1993) · Trends in Neurosciences · doi:10.1016/0166-2236(93)90007-9 · Cited by 181 · see citing works
Kuentzel, S. L., Ali, S. M., Altman, R. A., Greenberg, B. D., & Raub, T. J. (1993) · Biochemical Journal · doi:10.1042/bj2950367 · Cited by 134 · see citing works
Haass, C., Koo, E. H., Capell, A., Teplow, D. B., & Selkoe, D. J. (1995) · The Journal of Cell Biology · doi:10.1083/jcb.128.4.537 · Cited by 129 · see citing works
Self-citationKnops, J., Suomensaari, S., Lee, M., McConlogue, L., Seubert, P. A., & Sinha, S. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.6.2419 · Cited by 115 · see citing works
Self-citationHaass, C., Capell, A., Citron, M., Teplow, D. B., & Selkoe, D. J. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.11.6186 · Cited by 93 · see citing works
Self-citationFelsenstein, K. M., Hunihan, L. W., & Roberts, S. B. (1994) · Nature Genetics · doi:10.1038/ng0394-251 · Cited by 90 · see citing works
Strooper, B. D., Craessaerts, K., Dewachter, I., Moechars, D., Greenberg, B., LEUVEN, F. V., & BERGHE, H. V. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.8.4058 · Cited by 63 · see citing works
Metabolism of the “Swedish” amyloid precursor protein variant in Madin-Darby canine kidney cells.
Lo, A., Haass, C., Wagner, S. L., Teplow, D. B., & Sisodia, S. S. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47376-0 · Cited by 53 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
Alzheimer's Disease: Genes, Proteins, and Therapy
Selkoe, D. J. (2001) · Physiological Reviews · doi:10.1152/physrev.2001.81.2.741 · Cited by 6,063 · see citing works
Self-citationVassar, R., Bennett, B. D., Babu-Khan, S., Kahn, S., Mendiaz, E. A., Denis, P., Teplow, D. B., Ross, S., Amarante, P., Loeloff, R., et al. (1999) · Science · doi:10.1126/science.286.5440.735 · Cited by 3,876 · see citing works
Self-citationPathways towards and Away from Alzheimer’s Disease
Mattson, M. P. (2004) · Nature · doi:10.1038/nature02621 · Cited by 3,052 · see citing works
Amyloid Beta: Structure, Biology and Structure-Based Therapeutic Development
Chen, G.-F., Xu, T.-H., Yan, Y., Zhou, Y.-R., Jiang, Y., Melcher, K., & Xu, H. E. (2017) · Acta Pharmacologica Sinica · doi:10.1038/aps.2017.28 · Cited by 1,965 · see citing works
Intracellular amyloid-β in Alzheimer's disease
LaFerla, F. M., Green, K. N., & Oddo, S. (2007) · Nature Reviews Neuroscience · doi:10.1038/nrn2168 · Cited by 1,942 · see citing works
Translating cell biology into therapeutic advances in Alzheimer's disease
Selkoe, D. J. (1999) · Nature · doi:10.1038/399a023 · Cited by 1,588 · see citing works
Self-citationAlzheimer’s disease β-amyloid peptides are released in association with exosomes
Rajendran, L., Honsho, M., Zahn, T. R., Keller, P., Geiger, K. D., Verkade, P., & Simons, K. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0603838103 · Cited by 1,343 · see citing works
Citron, M., Westaway, D., Xia, W., Carlson, G., Diehl, T., Levesque, G., Johnson-wood, K., Lee, M., Seubert, P., Davis, A., et al. (1997) · Nature Medicine · doi:10.1038/nm0197-67 · Cited by 1,271 · see citing works
Self-citationIdentification of a Novel Aspartic Protease (Asp 2) as β-Secretase
Hussain, I., Powell, D., Howlett, D. R., Tew, D. G., Meek, T. D., Chapman, C., Gloger, I. S., Murphy, K. E., Southan, C. D., Ryan, D. M., et al. (1999) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.1999.0811 · Cited by 1,080 · see citing works
Trafficking and Proteolytic Processing of APP
Haass, C., Kaether, C., Thinakaran, G., & Sisodia, S. (2012) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a006270 · Cited by 1,075 · see citing works
Self-citationMolecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease
Guo, T., Zhang, D., Zeng, Y., Huang, T. Y., Xu, H., & Zhao, Y. (2020) · Molecular Neurodegeneration · doi:10.1186/s13024-020-00391-7 · Cited by 994 · see citing works
Efficient introduction of specific homozygous and heterozygous mutations using CRISPR/Cas9
Paquet, D., Kwart, D., Chen, A., Sproul, A., Jacob, S., Teo, S., Olsen, K. M., Gregg, A., Noggle, S., & Tessier-Lavigne, M. (2016) · Nature · doi:10.1038/nature17664 · Cited by 951 · see citing works
Gervais, F. G., Xu, D., Robertson, G. S., Vaillancourt, J. P., Zhu, Y., Huang, J., LeBlanc, A. C., Smith, D., Rigby, M., Shearman, M. S., et al. (1999) · Cell · doi:10.1016/s0092-8674(00)80748-5 · Cited by 783 · see citing works
Proteolytic processing and cell biological functions of the amyloid precursor protein
Strooper, B. D., & Annaert, W. G. (2000) · Journal of Cell Science · doi:10.1242/jcs.113.11.1857 · Cited by 628 · see citing works
Kuhn, P., Wang, H., Dislich, B., Colombo, A., Zeitschel, U., Ellwart, J. W., Kremmer, E., Roßner, S., & Lichtenthaler, S. F. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.167 · Cited by 621 · see citing works
MUTANT GENES IN FAMILIAL ALZHEIMER'S DISEASE AND TRANSGENIC MODELS
Price, D. L., & Sisodia, S. S. (1998) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.21.1.479 · Cited by 568 · see citing works
The Alzheimer's disease Beta-secretase enzyme, BACE1
Cole, S. L., & Vassar, R. (2007) · Molecular Neurodegeneration · doi:10.1186/1750-1326-2-22 · Cited by 550 · see citing works
Regulation of APP cleavage by α‐, β‐ and γ‐secretases
Nunan, J., & Small, D. H. (2000) · FEBS Letters · doi:10.1016/s0014-5793(00)02076-7 · Cited by 509 · see citing works
Dinkins, M. B., Dasgupta, S., Wang, G., Zhu, G., & Bieberich, E. (2014) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2014.02.012 · Cited by 494 · see citing works
PrionsPreprint
Colby, D. W., & Prusiner, S. B. (2011) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006833 · Cited by 469 · see citing works
Häfner, H., & der Heiden, W. A. (1997) · The Canadian Journal of Psychiatry · doi:10.1177/070674379704200204 · Cited by 437 · see citing works
Targeting protein aggregation for the treatment of degenerative diseases
Eisele, Y. S., Monteiro, C., Fearns, C., Encalada, S. E., Wiseman, R. L., Powers, E. T., & Kelly, J. W. (2015) · Nature Reviews Drug Discovery · doi:10.1038/nrd4593 · Cited by 416 · see citing works
ALZHEIMER'S DISEASE: Genetic Studies and Transgenic Models
Price, D. L., Tanzi, R. E., Borchelt, D. R., & Sisodia, S. S. (1998) · Annual Review of Genetics · doi:10.1146/annurev.genet.32.1.461 · Cited by 406 · see citing works
η-Secretase processing of APP inhibits neuronal activity in the hippocampus
Willem, M., Tahirovic, S., Busche, M. A., Ovsepian, S. V., Chafai, M., Kootar, S., Hornburg, D., Evans, L. D. B., Moore, S., Daria, A., et al. (2015) · Nature · doi:10.1038/nature14864 · Cited by 398 · see citing works
Self-citationCataldo, A. M., Barnett, J. L., Pieroni, C., & Nixon, R. A. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-16-06142.1997 · Cited by 393 · see citing works
BACE1: The β-Secretase Enzyme in Alzheimer's Disease
Vassar, R. J. (2004) · Journal of Molecular Neuroscience · doi:10.1385/jmn:23:1-2:105 · Cited by 369 · see citing works
BACE1 (β-secretase) inhibitors for the treatment of Alzheimer's disease
Ghosh, A. K., & Osswald, H. L. (2014) · Chemical Society Reviews · doi:10.1039/c3cs60460h · Cited by 361 · see citing works
Portelius, E., Bogdanovic, N., Gustavsson, M. K., Volkmann, I., Brinkmalm, G., Zetterberg, H., Winblad, B., & Blennow, K. (2010) · Acta Neuropathologica · doi:10.1007/s00401-010-0690-1 · Cited by 348 · see citing works
Maturation and Endosomal Targeting of β-Site Amyloid Precursor Protein-cleaving Enzyme
Huse, J. T., Pijak, D. S., Leslie, G. J., Lee, V. M.-Y., & Doms, R. W. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m004175200 · Cited by 402 · see citing works
Molecular Mechanisms of Disease-Causing Missense Mutations
Stefl, S. K., Nishi, H., Petukh, M. G., Panchenko, A. R., & Alexov, E. G. (2013) · Journal of Molecular Biology · doi:10.1016/j.jmb.2013.07.014 · Cited by 334 · see citing works
Vassar, R. J., Kuhn, P., Haass, C., Kennedy, M. E., Rajendran, L., Wong, P. C., & Lichtenthaler, S. F. (2014) · Journal of Neurochemistry · doi:10.1111/jnc.12715 · Cited by 329 · see citing works
Self-citationCapell, A., Grünberg, J., Pesold, B., Diehlmann, A., Citron, M., Nixon, R. A., Beyreuther, K. T., Selkoe, D. J., & Haass, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.6.3205 · Cited by 322 · see citing works
Self-citationSorting through the Cell Biology of Alzheimer's Disease: Intracellular Pathways to Pathogenesis
Small, S. A., & Gandy, S. (2006) · Neuron · doi:10.1016/j.neuron.2006.09.001 · Cited by 320 · see citing works
Metabolism of the “Swedish” Amyloid Precursor Protein Variant in Neuro2a (N2a) Cells
Thinakaran, G., Teplow, D. B., Siman, R., Greenberg, B., & Sisodia, S. S. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.16.9390 · Cited by 317 · see citing works
Annaert, W. G., Lévesque, L., Craessaerts, K., Dierinck, I., Snellings, G., Westaway, D. A., George‐Hyslop, P. S., Cordell, B., Fraser, P., & Strooper, B. D. (1999) · The Journal of Cell Biology · doi:10.1083/jcb.147.2.277 · Cited by 311 · see citing works
The amyloid cascade hypothesis: an updated critical review
Kepp, K. P., Robakis, N. K. R. K., Høilund‐Carlsen, P. F., Sensi, S. L., & Vissel, B. (2023) · Brain · doi:10.1093/brain/awad159 · Cited by 294 · see citing works
Acetylcholinesterase inhibitors: novel activities of old molecules
Racchi, M. (2004) · Pharmacological Research · doi:10.1016/j.phrs.2003.12.027 · Cited by 291 · see citing works
Citron, M., Diehl, T. S., Gordon, G., Biere, A. L., Seubert, P. A., & Selkoe, D. J. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.23.13170 · Cited by 287 · see citing works
Self-citationStrooper, B. D., Beullens, M., Contreras, B., Lévesque, L., Craessaerts, K., Cordell, B., Moechars, D., Bollen, M., Fraser, P., George‐Hyslop, P. S., et al. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.6.3590 · Cited by 286 · see citing works
Xu, H., Sweeney, D. A., Wang, R., Thinakaran, G., Lo, A., Sisodia, S. S., Greengard, P., & Gandy, S. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.3748 · Cited by 281 · see citing works
Weggen, S., Eriksen, J. L., Sagi, S. A., Pietrzik, C. U., Ozols, V. V., Fauq, A. H., Golde, T. E., & Koo, E. H. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m303592200 · Cited by 280 · see citing works
Balez, R., Steiner, N., Engel, M., Muñoz, S. S., Lum, J. S., Wu, Y., Wang, D., Vallotton, P., Sachdev, P. S., O’Connor, M. D., et al. (2016) · Scientific Reports · doi:10.1038/srep31450 · Cited by 278 · see citing works
Molecular genetics of Alzheimer’s disease
George‐Hyslop, P. S. (2000) · Biological Psychiatry · doi:10.1016/s0006-3223(99)00301-7 · Cited by 276 · see citing works
Larson, J., LYNCH, G. S., Games, D., & Seubert, P. A. (1999) · Brain Research · doi:10.1016/s0006-8993(99)01698-4 · Cited by 274 · see citing works
Self-citationA Therapeutic Antibody Targeting BACE1 Inhibits Amyloid-β Production in Vivo
Atwal, J. K., Chen, Y., Chiu, C., Mortensen, D. L., Meilandt, W. J., Liu, Y., Heise, C. E., Hoyte, K., Luk, W., Lu, Y., et al. (2011) · Science Translational Medicine · doi:10.1126/scitranslmed.3002254 · Cited by 274 · see citing works
Phosphorylation Regulates Intracellular Trafficking of β-Secretase
Walter, J., Fluhrer, R., Hartung, B., Willem, M., Kaether, C., Capell, A., Lammich, S., Multhaup, G., & Haass, C. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m011116200 · Cited by 272 · see citing works
Self-citationVPS35 haploinsufficiency increases Alzheimer’s disease neuropathology
Wen, L., Tang, F., Hong, Y., Luo, S.-W., Wang, C.-L., He, W., Shen, C., Jung, J.-U., Xiong, F., Lee, D.-H., et al. (2011) · The Journal of Cell Biology · doi:10.1083/jcb.201105109 · Cited by 264 · see citing works
Schlepckow, K., Kleinberger, G., Fukumori, A., Feederle, R., Lichtenthaler, S. F., Steiner, H., & Haass, C. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201707672 · Cited by 258 · see citing works
Self-citationKinoshita, A., Fukumoto, H., Shah, T., Whelan, C. M., Irizarry, M. C., & Hyman, B. T. (2003) · Journal of Cell Science · doi:10.1242/jcs.00643 · Cited by 284 · see citing works
Maturation and Pro-peptide Cleavage of β-Secretase
Capell, A., Steiner, H., Willem, M., Kaiser, H., Meyer, C., Walter, J., Lammich, S., Multhaup, G., & Haass, C. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.m003202200 · Cited by 247 · see citing works
Self-citationXia, W., Zhang, J., Perez, R. G., Koo, E. H., & Selkoe, D. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.15.8208 · Cited by 236 · see citing works
Self-citationJNK3 Perpetuates Metabolic Stress Induced by Aβ Peptides
Yoon, S. O., Park, D. J., Ryu, J. C., Özer, H. G., Tep, C., Shin, Y. J., Lim, T. H., Pastorino, L., Kunwar, A. J., Walton, J. C., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.06.024 · Cited by 236 · see citing works
Mastrangelo, M. A., & Bowers, W. J. (2008) · BMC Neuroscience · doi:10.1186/1471-2202-9-81 · Cited by 233 · see citing works
Walter, J., Capell, A., Grünberg, J., Pesold, B., Schindzielorz, A., Prior, R., Podlisny, M. B., Fraser, P., George‐Hyslop, P. S., Selkoe, D. J., et al. (1996) · Molecular Medicine · doi:10.1007/bf03401652 · Cited by 225 · see citing works
Self-citationAxonal Transport, Amyloid Precursor Protein, Kinesin-1, and the Processing Apparatus: Revisited
Lazarov, O., Morfini, G. A., Lee, E. B., Farah, M. H., Szodorai, A., DeBoer, S. R., Koliatsos, V. E., Kins, S., Lee, V. M. ‐., Wong, P. C., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.3089-04.2005 · Cited by 221 · see citing works
Updates in Alzheimer's disease: from basic research to diagnosis and therapies
Liu, E., Zhang, Y., & Wang, J. (2024) · Translational Neurodegeneration · doi:10.1186/s40035-024-00432-x · Cited by 220 · see citing works
Peng, S., Garzon, D. J., Marchese, M., Klein, W. L., Ginsberg, S. D., Francis, B. M., Mount, H. T. J., Mufson, E. J., Salehi, A., & Fahnestock, M. L. (2009) · Journal of Neuroscience · doi:10.1523/jneurosci.4736-08.2009 · Cited by 216 · see citing works
The role of APP and BACE1 trafficking in APP processing and amyloid-β generation
Zhang, X., & Song, W. (2013) · Alzheimer s Research & Therapy · doi:10.1186/alzrt211 · Cited by 216 · see citing works
Behavioral assays with mouse models of Alzheimer's disease: Practical considerations and guidelines
Puzzo, D., Lee, L. S., Palmeri, A., Calabrese, G., & Arancio, O. (2014) · Biochemical Pharmacology · doi:10.1016/j.bcp.2014.01.011 · Cited by 214 · see citing works
Ferroptosis as a mechanism of neurodegeneration in Alzheimer's disease
Jakaria, M., Belaidi, A. A., Bush, A. I., & Ayton, S. (2021) · Journal of Neurochemistry · doi:10.1111/jnc.15519 · Cited by 212 · see citing works
Schneider, A., Rajendran, L., Honsho, M., Gralle, M., Donnert, G., Wouters, F. S., Hell, S. W., & Simons, M. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.5345-07.2008 · Cited by 210 · see citing works
Obregon, D. F., Rezai-Zadeh, K. P., Bai, Y., Sun, N., Hou, H., Ehrhart, J. C., Zeng, J., Mori, T., Arendash, G. W., Shytle, D., et al. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m600617200 · Cited by 210 · see citing works
β-Secretase (BACE) as a drug target for alzheimer’s disease
Vassar, R. J. (2002) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(02)00157-6 · Cited by 209 · see citing works
Alpha-secretase in Alzheimer’s disease: molecular identity, regulation and therapeutic potential
Lichtenthaler, S. F. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.07081.x · Cited by 207 · see citing works
Lipid Rafts and Alzheimer’s Disease: Protein-Lipid Interactions and Perturbation of Signaling
Hicks, D. A., Nalivaeva, N. N., & Turner, A. J. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00189 · Cited by 205 · see citing works
Borg, J.-P., Yang, Y., De Taddéo-Borg, M., Margolis, B., & Turner, R. S. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.24.14761 · Cited by 201 · see citing works
Roßner, S., Sastre, M., Bourne, K. Z., & Lichtenthaler, S. F. (2006) · Progress in Neurobiology · doi:10.1016/j.pneurobio.2006.06.001 · Cited by 196 · see citing works
Roßner, S. (1998) · Progress in Neurobiology · doi:10.1016/s0301-0082(98)00044-6 · Cited by 195 · see citing works
Steiner, H., Capell, A., Pesold, B., Citron, M., Kloetzel, P. M., Selkoe, D. J., Romig, H., Mendla, K. D., & Haass, C. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.48.32322 · Cited by 194 · see citing works
Self-citationSennvik, K., Fastbom, J., Blomberg, M. E., Wahlund, L., Winblad, B., & Benedikz, E. (2000) · Neuroscience Letters · doi:10.1016/s0304-3940(99)00929-5 · Cited by 193 · see citing works
Weggen, S., & Beher, D. (2012) · Alzheimer's Research & Therapy · doi:10.1186/alzrt107 · Cited by 192 · see citing works
Zhang, C. M., Browne, A., Child, D. D., & Tanzi, R. E. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.133520 · Cited by 190 · see citing works
The β-Secretase, BACE: A Prime Drug Target for Alzheimer's Disease
Vassar, R. J. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:157 · Cited by 186 · see citing works
Heparan sulfate regulates amyloid precursor protein processing by BACE1, the Alzheimer's β-secretase
Scholefield, Z., Yates, E. A., Wayne, G., Amour, A., McDowell, W., & Turnbull, J. E. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200303059 · Cited by 182 · see citing works
Expression of Liver X Receptor Target Genes Decreases Cellular Amyloid β Peptide Secretion
Sun, Y., Yao, J., Kim, T.-W., & Tall, A. R. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300760200 · Cited by 179 · see citing works
Aβ Toxicity in Alzheimer's Disease
Cavallucci, V., D’Amelio, M., & Cecconi, F. (2012) · Molecular Neurobiology · doi:10.1007/s12035-012-8251-3 · Cited by 177 · see citing works
Marques, C. A., Keil, U., Bonert, A., Steiner, B., Haass, C., Müller, W. E., & Eckert, A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m212265200 · Cited by 175 · see citing works
Self-citationModifications and Trafficking of APP in the Pathogenesis of Alzheimer’s Disease
Wang, X., Zhou, X., Li, G., Zhang, Y., Wu, Y., & Song, W. (2017) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2017.00294 · Cited by 173 · see citing works
Sphingolipids: Critical players in Alzheimer’s disease
van Echten‐Deckert, G., & Walter, J. (2012) · Progress in Lipid Research · doi:10.1016/j.plipres.2012.07.001 · Cited by 172 · see citing works
Glutaminyl cyclases unfold glutamyl cyclase activity under mild acid conditions
Schilling, S., Hoffmann, T., Manhart, S., Hoffmann, M., & Demuth, H. (2004) · FEBS Letters · doi:10.1016/s0014-5793(04)00300-x · Cited by 172 · see citing works
Epigenetic Alterations in Alzheimer’s Disease
Sanchez-Mut, J. V., & Gräff, J. (2015) · Frontiers in Behavioral Neuroscience · doi:10.3389/fnbeh.2015.00347 · Cited by 168 · see citing works
Xiao, Q., Gil, S.-C., Yan, P., Wang, Y., Han, S., Gonzales, E., Perez, R., Cirrito, J. R., & Lee, J.-M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.338376 · Cited by 166 · see citing works
The physiology of the β‐amyloid precursor protein intracellular domain AICD
Pardossi‐Piquard, R., & Checler, F. (2011) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2011.07475.x · Cited by 160 · see citing works
The cell biology of Alzheimer's disease: uncovering the secrets of secretases
Walter, J., Kaether, C., Steiner, H., & Haass, C. (2001) · Current Opinion in Neurobiology · doi:10.1016/s0959-4388(00)00253-1 · Cited by 160 · see citing works
Self-citationASP1 (BACE2) Cleaves the Amyloid Precursor Protein at the β-Secretase Site
Hussain, I., Powell, D. J., Howlett, D. R., Chapman, G. A., Gilmour, L., Murdock, P. R., Tew, D. G., Meek, T. D., Chapman, C. G., Schneider, K., et al. (2000) · Molecular and Cellular Neuroscience · doi:10.1006/mcne.2000.0884 · Cited by 156 · see citing works
Vetrivel, K. S., Meckler, X., Chen, Y., Nguyen, P. D., Seidah, N. G., Vassar, R., Wong, P. C., Fukata, M., Kounnas, M. Z., & Thinakaran, G. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808920200 · Cited by 153 · see citing works
Kaether, C., Schmitt, S., Willem, M., & Haass, C. (2006) · Traffic · doi:10.1111/j.1600-0854.2006.00396.x · Cited by 148 · see citing works
Self-citationJonghe, C. D., Zehr, C., Yager, D., Prada, C.-M., Younkin, S. G., Hendriks, L., Broeckhoven, C. V., & Eckman, C. B. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0202 · Cited by 147 · see citing works
Presenilin-1 differentially facilitates endoproteolysis of the β-amyloid precursor protein and Notch
Capell, A., Steiner, H., Romig, H., Keck, S., Baader, M., Grim, M. G., Baumeister, R., & Haass, C. (2000) · Nature Cell Biology · doi:10.1038/35008626 · Cited by 147 · see citing works
Self-citationA metabolomic study of the CRND8 transgenic mouse model of Alzheimer's disease
Salek, R. M., Xia, J., Innes, A. E., Sweatman, B. C., Adalbert, R., Randle, S. J., McGowan, E. M., Emson, P. C., & Griffin, J. L. (2010) · Neurochemistry International · doi:10.1016/j.neuint.2010.04.001 · Cited by 146 · see citing works
Rosenberg, R. N., Lambracht‐Washington, D., Yu, G., & Xia, W. (2016) · JAMA Neurology · doi:10.1001/jamaneurol.2016.0301 · Cited by 145 · see citing works
CHIP and HSPs interact with β-APP in a proteasome-dependent manner and influence Aβ metabolism
Kumar, P., Ambasta, R. K., Veereshwarayya, V., Rosen, K. M., Kosik, K. S., Band, H., Mestril, R., Patterson, C., & Querfurth, H. W. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm030 · Cited by 145 · see citing works
González-Marrero, I., Giménez‐Llort, L., Johanson, C. E., Carmona-Calero, E. M., Castañeyra-Ruiz, L., Armas, J. M. B., Castañeyra-Perdomo, A., & Castro-Fuentes, R. (2015) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2015.00017 · Cited by 140 · see citing works
Amyloid precursor protein processing and retinal pathology in mouse models of Alzheimer’s disease
Dutescu, R. M., Li, Q., Crowston, J. G., Masters, C. L., Baird, P. N., & Culvenor, J. G. (2009) · Graefe s Archive for Clinical and Experimental Ophthalmology · doi:10.1007/s00417-009-1060-3 · Cited by 139 · see citing works
Getting to NO Alzheimer’s Disease: Neuroprotection versus Neurotoxicity Mediated by Nitric Oxide
Balez, R., & Ooi, L. (2015) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2016/3806157 · Cited by 138 · see citing works
Accelerated A Deposition in APPswe/PS1 E9 Mice with Hemizygous Deletions of TTR (Transthyretin)
Choi, S. H., Leight, S. N., Lee, V. M. ‐., Li, T., Wong, P. C., Johnson, J. A., Saraiva, M. J., & Sisodia, S. S. (2007) · Journal of Neuroscience · doi:10.1523/jneurosci.1919-07.2007 · Cited by 138 · see citing works
Tienari, P. J., Ida, N., Ikonen, E., Simons, M., Weidemann, A., Multhaup, G., Masters, C. L., Dotti, C. G., & Beyreuther, K. T. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.8.4125 · Cited by 138 · see citing works
Chyung, A. S. C., Greenberg, B., Cook, D. G., Doms, R. W., & Lee, V. M. ‐. (1997) · The Journal of Cell Biology · doi:10.1083/jcb.138.3.671 · Cited by 136 · see citing works
Secretase Targets for Alzheimer's Disease: Identification and Therapeutic Potential
Wolfe, M. S. (2001) · Journal of Medicinal Chemistry · doi:10.1021/jm0004897 · Cited by 133 · see citing works
Qiu, Z. J., Strickland, D. K., Hyman, B. T., & Rebeck, G. W. (1999) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.1999.0731393.x · Cited by 131 · see citing works
- Authors
- Haass, C., Lemere, C. A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L., & Selkoe, D. J.
- Affiliations
- Brigham and Women's Hospital (US)
- Karolinska Institutet (SE)
- Venue
- Nature Medicine
- Published
- 1995-12
- Volume
- 1
- Issue
- 12
- Pages
- 1291-1296
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2034504333
- Cited by
- 592
- References
- 33
- Citations by year
- 2026: 20 · 2025: 14 · 2024: 24 · 2023: 28 · 2022: 19 · 2021: 27 · 2020: 13 · 2019: 23 · 2018: 11 · 2017: 18 · 2016: 21 · 2015: 19 · 2014: 21 · 2013: 29 · 2012: 30
- FWCI
- 12.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG 12749, AG-06173, R01AG012749)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Swedish mutation, early-onset Alzheimer's disease, amyloid precursor protein, alpha-secretase, Golgi-derived vesicles, secretory pathway, secretory vesicles
- MeSH terms
- Aged, Alzheimer Disease, Amino Acid Sequence, Brain, Golgi Apparatus, Humans, Molecular Sequence Data, Mutation, Endopeptidases, Sweden, Amyloid beta-Peptides, Aspartic Acid Endopeptidases, Amyloid beta-Protein Precursor, Age of Onset, Amyloid Precursor Protein Secretases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review