An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp 717 ) Mutants

Suzuki, Nobuhiro; Cheung, Tobun T.; Cai, Xiao-Dan; Odaka, Asano; Otvos, Laszlo; Eckman, Christopher; Golde, Todd E.; Younkin, Steven G.

doi:10.1126/science.8191290

Cited by 1,471Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp 717 ) Mutants

Suzuki, Nobuhiro, Cheung, Tobun T., Cai, Xiao-Dan, Odaka, Asano, Otvos, Laszlo, Eckman, Christopher, Golde, Todd E., Younkin, Steven G.·1994·Science

DOI 10.1126/science.8191290

Open this paper in CoChat — free account

Abstract

Normal processing of the amyloid β protein precursor (βAPP) results in secretion of a soluble 4-kilodalton protein essentially identical to the amyloid β protein (Aβ) that forms insoluble fibrillar deposits in Alzheimer's disease. Human neuroblastoma (M17) cells transfected with constructs expressing wild-type βAPP or the βAPP 717 mutants linked to familial Alzheimer's disease were compared by (i) isolation of metabolically labeled 4-kilodalton Aβ from conditioned medium, digestion with cyanogen bromide, and analysis of the carboxyl-terminal peptides released, or (ii) analysis of the Aβ in conditioned medium with sandwich enzyme-linked immunosorbent assays that discriminate Aβ 1-40 from the longer Aβ 1-42 . Both methods demonstrated that the 4-kilodalton Aβ released from wild-type βAPP is primarily but not exclusively Aβ 1-40 . The βAPP 717 mutations, which are located three residues carboxyl to Aβ 43 , consistently caused a 1.5- to 1.9-fold increase in the percentage of longer Aβ generated. Long Aβ (for example, Aβ 1-42 ) forms insoluble amyloid fibrils more rapidly than Aβ 1-40 . Thus, the βAPP 717 mutants may cause Alzheimer's disease because they secrete increased amounts of long Aβ, thereby fostering amyloid deposition.

Integrity signals

Registry

Crossref · 10.1126/science.8191290

Cites

6 of 6 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

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 sandwich ELISAs used specifically detect Aβs ending at Aβ40 or at Aβ42(43).
“The monoclonal antibodies employed were BAN-50 (anti-A{31-16), 4G8 (anti-Af3l7-24) (19), BA-27, which is specific for A{3 ending at A{340, and BC-05, which is specific for A{3 ending at A{342(43).”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [9]
β-APP mutations (AI, AF) linked to familial AD increase the percentage of long Aβ1-42(43) secreted.
“Moreover, we have recently used transfected cultured cells to show that (3-APP mutations (AI, AF) linked to familial AD increase the percentage of long A{31-42(43) secreted (9).”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [9]
Aβs ending at Aβ42(43) are a minor component of the Aβ in human cerebrospinal fluid and plasma.
“These observations indicate that Aps ending at Ap42(43), which are a minor component of the Ap in human cerebrospinal fluid and”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [9]
Aβs ending at Aβ42(43) are critically important in AD where they deposit selectively in plaques of all kinds.
“These observations indicate that Aps ending at Ap42(43), which are a minor component of the Ap in human cerebrospinal fluid and plasma, are critically important in AD where they deposit selectively in plaques of all kinds.”
From Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain (1995) · cites this paper as [9]
Secreted Aβ is readily detected in CSF, plasma, and medium conditioned by a wide variety of cultured cells.
“Secreted A␤ is readily detected in CSF, plasma, and in medium conditioned by a wide variety of cultured cells”
From Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease (2001) · cites this paper as Suzuki et al., 1994

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
Mutation of the β-amyloid precursor protein in familial Alzheimer's disease increases β-protein production
Citron, 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
Amyloid β Protein Gene: cDNA, mRNA Distribution, and Genetic Linkage Near the Alzheimer Locus
Tanzi, R. E., Gusella, J. F., Watkins, P. C., Bruns, G. A. P., St George-Hyslop, P., Van Keuren, M. L., Patterson, D., Pagan, S., Kurnit, D. M., & Neve, R. L. (1987) · Science · doi:10.1126/science.2949367 · Cited by 1,611 · 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
Self-citation
Assembly and aggregation properties of synthetic Alzheimer's A4/beta amyloid peptide analogs.
Burdick, D., Soreghan, B., Kwon, M., Kosmoski, J., Knauer, M., Henschen, A., Yates, J., Cotman, C., & Glabe, C. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)48529-8 · Cited by 1,014 · see citing works
Cells with a familial Alzheimerʼs disease mutation produce authentic β-peptide
Dovey, H. F., Suomensaari-Chrysler, S., Lieberburg, I., Sinha, S., & Keim, P. S. (1993) · NeuroReport · doi:10.1097/00001756-199308000-00011 · Cited by 71 · see citing works

Flagged first, then by citations

Sorted by citations

The Amyloid Hypothesis of Alzheimer’s Disease: Progress and Problems on the Road to Therapeutics
Hardy, J., & Selkoe, D. J. (2002) · Science · doi:10.1126/science.1072994 · Cited by 13,864 · see citing works
Soluble protein oligomers in neurodegeneration: lessons from the Alzheimer's amyloid β-peptide
Haass, C., & Selkoe, D. J. (2007) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2101 · Cited by 4,744 · see citing works
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G. (1996) · Science · doi:10.1126/science.274.5284.99 · Cited by 4,210 · see citing works
Self-citation
Triple-Transgenic Model of Alzheimer’s Disease with Plaques and Tangles
Oddo, S., Caccamo, A., Shepherd, J. D., Murphy, M. P., Golde, T. E., Kayed, R., Metherate, R., Mattson, M. P., Akbari, Y., & LaFerla, F. M. (2003) · Neuron · doi:10.1016/s0896-6273(03)00434-3 · Cited by 4,126 · see citing works
Self-citation
Diffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506 · see citing works
Immunization with amyloid-β attenuates Alzheimer-disease-like pathology in the PDAPP mouse
Schenk, D., Barbour, R., Dunn, W., Gordon, G., Grajeda, H., Guido, T., Hu, K., Huang, J., Johnson-Wood, K., Khan, K., et al. (1999) · Nature · doi:10.1038/22124 · Cited by 3,160 · see citing works
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
Scheuner, D., Eckman, C., Jensen, M., Song, X., Citron, M., Suzuki, N., Bird, T. D., Hardy, J., Hutton, M., Kukull, W., et al. (1996) · Nature Medicine · doi:10.1038/nm0896-864 · Cited by 2,599 · see citing works
Self-citation
Alzheimer-type neuropathology in transgenic mice overexpressing V717F β-amyloid precursor protein
Games, D., Adams, D., Alessandrini, R., Barbour, R., Borthelette, P., Blackwell, C., Carr, T., Clemens, J., Donaldson, T., Gillespie, F., et al. (1995) · Nature · doi:10.1038/373523a0 · Cited by 2,516 · see citing works
Aβ Oligomers – a decade of discovery
Walsh, D. M., & Selkoe, D. J. (2007) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2006.04426.x · Cited by 1,938 · see citing works
Visualization of Aβ42(43) and Aβ40 in senile plaques with end-specific Aβ monoclonals: Evidence that an initially deposited species is Aβ42(43)
Iwatsubo, T., Odaka, A., Suzuki, N., Mizusawa, H., Nukina, N., & Ihara, Y. (1994) · Neuron · doi:10.1016/0896-6273(94)90458-8 · Cited by 1,774 · see citing works
Self-citation
APP Processing and Synaptic Function
Kamenetz, F., Tomita, T., Hsieh, H., Seabrook, G., Borchelt, D., Iwatsubo, T., Sisodia, S., & Malinow, R. (2003) · Neuron · doi:10.1016/s0896-6273(03)00124-7 · Cited by 1,644 · see citing works
Mutant presenilins specifically elevate the levels of the 42 residue β-amyloid peptide in vivo: evidence for augmentation of a 42-specific γ secretase
Jankowsky, J. L., Fadale, D. J., Anderson, J., Xu, G. M., Gonzales, V., Jenkins, N. A., Copeland, N. G., Lee, M. K., Younkin, L. H., Wagner, S. L., et al. (2004) · Human Molecular Genetics · doi:10.1093/hmg/ddh019 · Cited by 1,575 · see citing works
Self-citation
Two amyloid precursor protein transgenic mouse models with Alzheimer disease-like pathology
Sturchler-Pierrat, C., Abramowski, D., Duke, M., Wiederhold, K.-H., Mistl, C., Rothacher, S., Ledermann, B., Bürki, K., Frey, P., Paganetti, P. A., et al. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.24.13287 · Cited by 1,507 · see citing works
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80230-5 · Cited by 1,478 · see citing works
Self-citation
Membrane-anchored aspartyl protease with Alzheimer's disease β-secretase activity
Yan, R., Bienkowski, M. J., Shuck, M. E., Miao, H., Tory, M. C., Pauley, A. M., Brashler, J. R., Stratman, N. C., Mathews, W. R., Buhl, A. E., et al. (1999) · Nature · doi:10.1038/990107 · Cited by 1,438 · see citing works
The 'Arctic' APP mutation (E693G) causes Alzheimer's disease by enhanced Aβ protofibril formation
Nilsberth, C., Westlind-Danielsson, A., Eckman, C. B., Condron, M. M., Axelman, K., Forsell, C., Stenh, C., Luthman, J., Teplow, D. B., Younkin, S. G., et al. (2001) · Nature Neuroscience · doi:10.1038/nn0901-887 · Cited by 1,209 · see citing works
Self-citation
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
Review Article: Genetics of Alzheimer Disease
Bekris, L. M., Yu, C.-E., Bird, T. D., & Tsuang, D. W. (2010) · Journal of Geriatric Psychiatry and Neurology · doi:10.1177/0891988710383571 · Cited by 1,029 · see citing works
Age-Dependent Changes in Brain, CSF, and Plasma Amyloid β Protein in the Tg2576 Transgenic Mouse Model of Alzheimer's Disease
Kawarabayashi, T., Younkin, L. H., Saido, T. C., Shoji, M., Ashe, K. H., & Younkin, S. G. (2001) · The Journal of Neuroscience · doi:10.1523/jneurosci.21-02-00372.2001 · Cited by 1,053 · see citing works
“Studies of human plasma, human fibroblasts, transfected cells, and transgenic mice have shown that each of these genetic forms of AD either selectively increases the extracellular concentration of Ab42 ( Suzuki et al., 1994; Borchelt et al., 1996; Duff et al., 1996; Scheuner et al., 1996; Citron et al., 1997) or incre…”
BackgroundMethodInfluentialSelf-citation
Accelerated Amyloid Deposition in the Brains of Transgenic Mice Coexpressing Mutant Presenilin 1 and Amyloid Precursor Proteins
Borchelt, D. R., Ratovitski, T., van Lare, J., Lee, M. K., Gonzales, V., Jenkins, N. A., Copeland, N. G., Price, D. L., & Sisodia, S. S. (1997) · Neuron · doi:10.1016/s0896-6273(00)80974-5 · Cited by 1,023 · see citing works
Early-onset Amyloid Deposition and Cognitive Deficits in Transgenic Mice Expressing a Double Mutant Form of Amyloid Precursor Protein 695
Chishti, M. A., Yang, D.-S., Janus, C., Phinney, A. L., Horne, P., Pearson, J., Strome, R., Zuker, N., Loukides, J., French, J., et al. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m100710200 · Cited by 955 · see citing works
Impaired synaptic plasticity and learning in aged amyloid precursor protein transgenic mice
Chapman, P. F., White, G. L., Jones, M. W., Cooper-Blacketer, D., Marshall, V. J., Irizarry, M., Younkin, L., Good, M. A., Bliss, T. V. P., Hyman, B. T., et al. (1999) · Nature Neuroscience · doi:10.1038/6374 · Cited by 946 · see citing works
Self-citation
Environmental Enrichment Reduces Aβ Levels and Amyloid Deposition in Transgenic Mice
Lazarov, O., Robinson, J., Tang, Y.-P., Hairston, I. S., Korade-Mirnics, Z., Lee, V. M.-Y., Hersh, L. B., Sapolsky, R. M., Mirnics, K., & Sisodia, S. S. (2005) · Cell · doi:10.1016/j.cell.2005.01.015 · Cited by 885 · see citing works
Amyloid-associated proteins α1-antichymotrypsin and apolipoprotein E promote assembly of Alzheimer β-protein into filaments
Ma, J., Yee, A., Brewer, H. B., Das, S., & Potter, H. (1994) · Nature · doi:10.1038/372092a0 · Cited by 871 · see citing works
Cell biology of protein misfolding: the examples of Alzheimer's and Parkinson's diseases
Selkoe, D. J. (2004) · Nature Cell Biology · doi:10.1038/ncb1104-1054 · Cited by 863 · see citing works
Cu(II) Potentiation of Alzheimer Aβ Neurotoxicity
Huang, X., Cuajungco, M. P., Atwood, C. S., Hartshorn, M. A., Tyndall, J. D. A., Hanson, G. R., Stokes, K. C., Leopold, M., Multhaup, G., Goldstein, L. E., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.52.37111 · Cited by 762 · see citing works
BACE knockout mice are healthy despite lacking the primary beta-secretase activity in brain: Implications for Alzheimer’s disease therapeutics
Roberds, S. L. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.12.1317 · Cited by 705 · see citing works
The role of microglia in amyloid clearance from the AD brain
Lee, C. Y. D., & Landreth, G. E. (2010) · Journal of Neural Transmission · doi:10.1007/s00702-010-0433-4 · Cited by 701 · see citing works
The Aging Brain
Yankner, B. A., Lu, T., & Loerch, P. (2008) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathmechdis.2.010506.092044 · Cited by 677 · see citing works
Amyloid β Protein (Aβ) in Alzheimeri's Disease Brain
Gravina, S. A., Ho, L., Eckman, C. B., Long, K. E., Otvos, L., Younkin, L. H., Suzuki, N., & Younkin, S. G. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7013 · Cited by 676 · see citing works
Self-citation
NSAIDs and enantiomers of flurbiprofen target γ-secretase and lower Aβ42 in vivo
Eriksen, J. L., Sagi, S. A., Smith, T. E., Weggen, S., Das, P., McLendon, D. C., Ozols, V. V., Jessing, K. W., Zavitz, K. H., Koo, E. H., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci18162 · Cited by 634 · see citing works
Dominant and differential deposition of distinct β-amyloid peptide species, AβN3(pE), in senile plaques
Saido, T. C., Iwatsubo, T., Mann, D. M. A., Shimada, H., Ihara, Y., & Kawashima, S. (1995) · Neuron · doi:10.1016/0896-6273(95)90301-1 · Cited by 587 · see citing works
The Swedish mutation causes early-onset Alzheimer's disease by β-secretase cleavage within the secretory pathway
Haass, C., Lemere, C. A., Capell, A., Citron, M., Seubert, P., Schenk, D., Lannfelt, L., & Selkoe, D. J. (1995) · Nature Medicine · doi:10.1038/nm1295-1291 · Cited by 592 · see citing works
Synergistic Interactions between Aβ, Tau, and α-Synuclein: Acceleration of Neuropathology and Cognitive Decline
Clinton, L. K., Blurton-Jones, M., Myczek, K., Trojanowski, J. Q., & LaFerla, F. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.0490-10.2010 · Cited by 576 · see citing works
The Levels of Soluble versus Insoluble Brain Aβ Distinguish Alzheimer's Disease from Normal and Pathologic Aging
Wang, J., Dickson, D. W., Trojanowski, J. Q., & Lee, V. M.-Y. (1999) · Experimental Neurology · doi:10.1006/exnr.1999.7085 · Cited by 567 · see citing works
Amyloid β-Peptide Impairs Glucose Transport in Hippocampal and Cortical Neurons: Involvement of Membrane Lipid Peroxidation
Mark, R. J., Pang, Z., Geddes, J. W., Uchida, K., & Mattson, M. P. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-03-01046.1997 · Cited by 551 · see citing works
Current state of Alzheimer’s fluid biomarkers
Molinuevo, J. L., Ayton, S., Batrla, R., Bednar, M. M., Bittner, T., Cummings, J., Fagan, A. M., Hampel, H., Mielke, M. M., Mikulskis, A., et al. (2018) · Acta Neuropathologica · doi:10.1007/s00401-018-1932-x · Cited by 518 · see citing works
Neurotoxicity of Alzheimer’s disease Aβ peptides is induced by small changes in the Aβ42 to Aβ40 ratio
Kuperstein, I., Broersen, K., Benilova, I., Rozenski, J., Jonckheere, W., Debulpaep, M., Vandersteen, A., Segers‐Nolten, I., Van Der Werf, K., Subramaniam, V., et al. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.211 · Cited by 532 · see citing works
YKL-40: A Novel Prognostic Fluid Biomarker for Preclinical Alzheimer's Disease
Craig-Schapiro, R., Perrin, R. J., Roe, C. M., Xiong, C., Carter, D., Cairns, N. J., Mintun, M. A., Peskind, E. R., Li, G., Galasko, D. R., et al. (2010) · Biological Psychiatry · doi:10.1016/j.biopsych.2010.08.025 · Cited by 504 · see citing works
Involvement of Microglial Receptor for Advanced Glycation Endproducts (RAGE) in Alzheimer's Disease: Identification of a Cellular Activation Mechanism
Lue, L.-F., Walker, D. G., Brachova, L., Beach, T. G., Rogers, J., Schmidt, A. M., Stern, D. M., & Yan, S. D. (2001) · Experimental Neurology · doi:10.1006/exnr.2001.7732 · Cited by 439 · see citing works
Amyloid-β immunotherapy for Alzheimer's disease: the end of the beginning
Schenk, D. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn938 · Cited by 436 · see citing works
Increased neuronal endocytosis and protease delivery to early endosomes in sporadic Alzheimer’s disease: Neuropathologic evidence for a mechanism of increased β-amyloidogenesis
Cataldo, 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
Amyloid-beta aggregation: selective inhibition of aggregation in mixtures of amyloid with different chain lengths
Snyder, S. W., Ladror, U. S., Wade, W. S., Wang, G. T., Barrett, L. W., Matayoshi, E. D., Huffaker, H. J., Krafft, G. A., & Holzman, T. F. (1994) · Biophysical Journal · doi:10.1016/s0006-3495(94)80591-0 · Cited by 381 · see citing works
The familial Alzheimer's disease APPV717I mutation alters APP processing and Tau expression in iPSC-derived neurons
Muratore, C. R., Rice, H. C., Srikanth, P., Callahan, D. G., Shin, T., Benjamin, L. N. P., Walsh, D. M., Selkoe, D. J., & Young-Pearse, T. L. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu064 · Cited by 379 · see citing works
Oxidative stress precedes fibrillar deposition of Alzheimer's disease amyloid β-peptide (1–42) in a transgenic Caenorhabditis elegans model
Drake, J. (2003) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00225-7 · Cited by 371 · see citing works
Cerebrospinal Fluid Tau and β-Amyloid: How Well Do These Biomarkers Reflect Autopsy-Confirmed Dementia Diagnoses?
Clark, C. M., Xie, S., Chittams, J., Ewbank, D., Peskind, E., Galasko, D., Morris, J. C., McKeel, D. W., Farlow, M., Weitlauf, S. L., et al. (2003) · Archives of Neurology · doi:10.1001/archneur.60.12.1696 · Cited by 357 · see citing works
Evaluation of the safety and immunogenicity of synthetic Aβ42 (AN1792) in patients with AD
Bayer, A. J., Bullock, R., Jones, R. W., Wilkinson, D., Paterson, K. R., Jenkins, L., Millais, S. B., & Donoghue, S. (2005) · Neurology · doi:10.1212/01.wnl.0000148604.77591.67 · Cited by 356 · see citing works
Effects of PS1 Deficiency on Membrane Protein Trafficking in Neurons
Naruse, S., Thinakaran, G., Luo, J.-J., Kusiak, J. W., Tomita, T., Iwatsubo, T., Qian, X., Ginty, D. D., Price, D. L., Borchelt, D. R., et al. (1998) · Neuron · doi:10.1016/s0896-6273(00)80637-6 · Cited by 355 · see citing works
Repetitive Mild Brain Trauma Accelerates Aβ Deposition, Lipid Peroxidation, and Cognitive Impairment in a Transgenic Mouse Model of Alzheimer Amyloidosis
Uryu, K., Laurer, H., McIntosh, T., Praticò, D., Martinez, D., Leight, S., Lee, V. M.-Y., & Trojanowski, J. Q. (2002) · The Journal of Neuroscience · doi:10.1523/jneurosci.22-02-00446.2002 · Cited by 337 · see citing works
Amyloid β-Peptide Is Transported on Lipoproteins and Albumin in Human Plasma
Biere, A. L., Ostaszewski, B., Stimson, E. R., Hyman, B. T., Maggio, J. E., & Selkoe, D. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.51.32916 · Cited by 331 · see citing works
Melatonin increases survival and inhibits oxidative and amyloid pathology in a transgenic model of Alzheimer's disease
Matsubara, E., Bryant‐Thomas, T., Pacheco Quinto, J., Henry, T. L., Poeggeler, B., Herbert, D., Cruz‐Sanchez, F., Chyan, Y., Smith, M. A., Perry, G., et al. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01654.x · Cited by 332 · see citing works
Recognition of the amyloid precursor protein by human γ-secretase
Zhou, R., Yang, G., Guo, X., Zhou, Q., Lei, J., & Shi, Y. (2019) · Science · doi:10.1126/science.aaw0930 · Cited by 304 · see citing works
Intracellular Generation and Accumulation of Amyloid β-Peptide Terminating at Amino Acid 42
Wild-Bode, C., Yamazaki, T., Capell, A., Leimer, U., Steiner, H., Ihara, Y., & Haass, C. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.26.16085 · Cited by 303 · see citing works
Amino-terminal Deletions Enhance Aggregation of β-Amyloid Peptides in Vitro
Pike, C. J., Overman, M. J., & Cotman, C. W. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.41.23895 · Cited by 302 · see citing works
β-Secretase Activity Increases with Aging in Human, Monkey, and Mouse Brain
Fukumoto, H., Rosene, D. L., Moss, M. B., Raju, S., Hyman, B. T., & Irizarry, M. C. (2004) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)63159-8 · Cited by 294 · see citing works
Cerebrovascular autoregulation is profoundly impaired in mice overexpressing amyloid precursor protein
Niwa, K., Kazama, K., Younkin, L., Younkin, S. G., Carlson, G. A., & Iadecola, C. (2002) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00022.2002 · Cited by 286 · see citing works
Self-citation
Detection of a Novel Intraneuronal Pool of Insoluble Amyloid β Protein that Accumulates with Time in Culture
Skovronsky, D. M., Doms, R. W., & Lee, V. M.-Y. (1998) · The Journal of Cell Biology · doi:10.1083/jcb.141.4.1031 · Cited by 290 · see citing works
Retinoic Acid Attenuates β-Amyloid Deposition and Rescues Memory Deficits in an Alzheimer's Disease Transgenic Mouse Model
Ding, Y., Qiao, A., Wang, Z., Goodwin, J. S., Lee, E.-S., Block, M. L., Allsbrook, M., McDonald, M. P., & Fan, G.-H. (2008) · The Journal of Neuroscience · doi:10.1523/jneurosci.3153-08.2008 · Cited by 269 · see citing works
A Lack of Amyloid β Plaques Despite Persistent Accumulation of Amyloid β in Axons of Long‐Term Survivors of Traumatic Brain Injury
Chen, X., Johnson, V. E., Uryu, K., Trojanowski, J. Q., & Smith, D. H. (2009) · Brain Pathology · doi:10.1111/j.1750-3639.2008.00176.x · Cited by 267 · see citing works
High‐molecular‐weight β‐amyloid oligomers are elevated in cerebrospinal fluid of Alzheimer patients
Fukumoto, H., Tokuda, T., Kasai, T., Ishigami, N., Hidaka, H., Kondo, M., Allsop, D., & Nakagawa, M. (2010) · The FASEB Journal · doi:10.1096/fj.09-150359 · Cited by 264 · see citing works
Amyloid β interacts with the amyloid precursor protein: a potential toxic mechanism in Alzheimer's disease
Lorenzo, A., Yuan, M., Zhang, Z., Paganetti, P. A., Sturchler-Pierrat, C., Staufenbiel, M., Mautino, J., Vigo, F. S., Sommer, B., & Yankner, B. A. (2000) · Nature Neuroscience · doi:10.1038/74833 · Cited by 258 · see citing works
On the Seeding and Oligomerization of pGlu-Amyloid Peptides (in vitro)
Schilling, S., Lauber, T., Schaupp, M., Manhart, S., Scheel, E., Böhm, G., & Demuth, H.-U. (2006) · Biochemistry · doi:10.1021/bi0612667 · Cited by 254 · see citing works
Clearance mechanisms of Alzheimer's amyloid-β peptide: implications for therapeutic design and diagnostic tests
Bates, K. A., Verdile, G., Li, Q.-X., Ames, D., Hudson, P., Masters, C. L., & Martins, R. N. (2009) · Molecular Psychiatry · doi:10.1038/mp.2008.96 · Cited by 247 · see citing works
Genetics of β-Amyloid Precursor Protein in Alzheimer's Disease
TCW, J., & Goate, A. M. (2017) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a024539 · Cited by 242 · see citing works
Persistent Amyloidosis following Suppression of Aβ Production in a Transgenic Model of Alzheimer Disease
Jankowsky, J. L., Slunt, H. H., Gonzales, V., Savonenko, A. V., Wen, J. C., Jenkins, N. A., Copeland, N. G., Younkin, L. H., Lester, H. A., Younkin, S. G., et al. (2005) · PLoS Medicine · doi:10.1371/journal.pmed.0020355 · Cited by 237 · see citing works
Self-citation
Age-Related Amyloid β Deposition in Transgenic Mice Overexpressing Both Alzheimer Mutant Presenilin 1 and Amyloid β Precursor Protein Swedish Mutant Is Not Associated with Global Neuronal Loss
Takeuchi, A., Irizarry, M. C., Duff, K., Saido, T. C., Hsiao Ashe, K., Hasegawa, M., Mann, D. M. A., Hyman, B. T., & Iwatsubo, T. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64544-0 · Cited by 229 · see citing works
Pathogenic APP mutations near the gamma-secretase cleavage site differentially affect Abeta secretion and APP C-terminal fragment stability
De Jonghe, C. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.16.1665 · Cited by 223 · see citing works
Intracellular Mechanisms of Amyloid Accumulation and Pathogenesis in Alzheimer's Disease
Glabe, C. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:2:137 · Cited by 222 · see citing works
Alterations in cerebral blood flow and glucose utilization in mice overexpressing the amyloid precursor protein
Niwa, K., Kazama, K., Younkin, S. G., Carlson, G. A., & Iadecola, C. (2002) · Neurobiology of Disease · doi:10.1006/nbdi.2001.0460 · Cited by 218 · see citing works
Self-citation
Serotonin 5-HT2a and 5-HT2c Receptors Stimulate Amyloid Precursor Protein Ectodomain Secretion
Nitsch, R. M., Deng, M., Growdon, J. H., & Wurtman, R. J. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.8.4188 · Cited by 219 · see citing works
Increased susceptibility to ischemic brain damage in transgenic mice overexpressing the amyloid precursor protein
Zhang, F., Eckman, C., Younkin, S., Hsiao, K. K., & Iadecola, C. (1997) · The Journal of Neuroscience · doi:10.1523/jneurosci.17-20-07655.1997 · Cited by 205 · see citing works
Self-citation
Amyloid β Protein Starting Pyroglutamate at Position 3 Is a Major Component of the Amyloid Deposits in the Alzheimer's Disease Brain
Harigaya, Y., Saido, T. C., Eckman, C. B., Prada, C.-M., Shoji, M., & Younkin, S. G. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3490 · Cited by 202 · see citing works
Self-citation
Molecular Mechanisms and Genetics of Oxidative Stress in Alzheimer’s Disease
Cioffi, F., Adam, R. H. I., & Broersen, K. (2019) · Journal of Alzheimer s Disease · doi:10.3233/jad-190863 · Cited by 204 · see citing works
Structural basis of γ-secretase inhibition and modulation by small molecule drugs
Yang, G., Zhou, R., Guo, X., Yan, C., Lei, J., & Shi, Y. (2021) · Cell · doi:10.1016/j.cell.2020.11.049 · Cited by 189 · see citing works
The X11α protein slows cellular amyloid precursor protein processing and reduces Aβ40 and Aβ42 secretion
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
Reorganization of cholinergic terminals in the cerebral cortex and hippocampus in transgenic mice carrying mutated presenilin-1 and amyloid precursor protein transgenes
Wong, T. P., Debeir, T., Duff, K., & Cuello, A. C. (1999) · The Journal of Neuroscience · doi:10.1523/jneurosci.19-07-02706.1999 · Cited by 196 · see citing works
Neuronal Cell Death in Alzheimers Disease and a Neuroprotective Factor, Humanin
Niikura, T., Tajima, H., & Kita, Y. (2006) · Current Neuropharmacology · doi:10.2174/157015906776359577 · Cited by 184 · see citing works
Amyloid β protein (Aβ) deposition in chromosome 14–linked Alzheimer's disease: Predominance of Aβ42(43)
Mann, D. M. A., Iwatsubo, T., Cairns, N. J., Lantos, P. L., Nochlin, D., Sumi, S. M., Bird, T. D., Poorkaj, P., Hardy, J., Hutton, M., et al. (1996) · Annals of Neurology · doi:10.1002/ana.410400205 · Cited by 184 · see citing works
Amyloids and Are Generated Intracellularly in Cultured Human Neurons and Their Secretion Increases with Maturation
Turner, R. S., Suzuki, N., Chyung, A. S. C., Younkin, S. G., & Lee, V. M.-Y. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.15.8966 · Cited by 161 · see citing works
Self-citation
Genetic Modification of the Phenotypes Produced by Amyloid Precursor Protein Overexpression in Transgenic Mice
Carlson, G. A., Borchelt, D. R., Dake, A., Turner, S., Danielson, V., Coffin, J. D., Eckman, C., Meiners, J., Nilsen, S. P., Younkin, S. G., et al. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.11.1951 · Cited by 158 · see citing works
Self-citation
Nonfibrillar diffuse amyloid deposition due to a gamma42-secretase site mutation points to an essential role for N-truncated Abeta42 in Alzheimer's disease
Kumar-Singh, S. (2000) · Human Molecular Genetics · doi:10.1093/hmg/9.18.2589 · Cited by 158 · see citing works
Microvascular brain damage with aging and hypertension: pathophysiological consideration and clinical implications
Scuteri, A., Nilsson, P. M., Tzourio, C., Redon, J., & Laurent, S. (2011) · Journal of Hypertension · doi:10.1097/hjh.0b013e328347cc17 · Cited by 151 · see citing works
Enhanced Amyloidogenic Processing of the β-Amyloid Precursor Protein in Gene-targeted Mice Bearing the Swedish Familial Alzheimer's Disease Mutations and a “Humanized” Aβ Sequence
Reaume, A. G., Howland, D. S., Trusko, S. P., Savage, M. J., Lang, D. M., Greenberg, B. D., Siman, R., & Scott, R. W. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.38.23380 · Cited by 150 · see citing works
Brain Trauma Induces Massive Hippocampal Neuron Death Linked to a Surge in β-Amyloid Levels in Mice Overexpressing Mutant Amyloid Precursor Protein
Smith, D. H., Nakamura, M., McIntosh, T. K., Wang, J., Rodríguez, A., Chen, X.-H., Raghupathi, R., Saatman, K. E., Clemens, J., Schmidt, M. L., et al. (1998) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65643-x · Cited by 143 · see citing works
If amyloid drives Alzheimer disease, why have anti-amyloid therapies not yet slowed cognitive decline?
Haass, C., & Selkoe, D. (2022) · PLOS Biology · doi:10.1371/journal.pbio.3001694 · Cited by 145 · see citing works
Amyloid beta-protein reduces acetylcholine synthesis in a cell line derived from cholinergic neurons of the basal forebrain.
Pedersen, W. A., Kloczewiak, M. A., & Blusztajn, J. K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.15.8068 · Cited by 134 · see citing works
Presenilin-1 P264L Knock-In Mutation: Differential Effects on Aβ Production, Amyloid Deposition, and Neuronal Vulnerability
Siman, R., Reaume, A. G., Savage, M. J., Trusko, S., Lin, Y.-G., Scott, R. W., & Flood, D. G. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-23-08717.2000 · Cited by 133 · see citing works
Age and Apolipoprotein E*4 Allele Effects on Cerebrospinal Fluid β-Amyloid 42 in Adults With Normal Cognition
Peskind, E. R., Li, G., Shofer, J., Quinn, J. F., Kaye, J. A., Clark, C. M., Farlow, M. R., DeCarli, C., Raskind, M. A., Schellenberg, G. D., et al. (2006) · Archives of Neurology · doi:10.1001/archneur.63.7.936 · Cited by 131 · see citing works
β-Amyloid (Aβ) Deposition in the Brains of Aged Orangutans
Gearing, M., Tigges, J., Mori, H., & Mirra, S. S. (1997) · Neurobiology of Aging · doi:10.1016/s0197-4580(97)00012-2 · Cited by 130 · see citing works
Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice
Lamb, B. (1997) · Human Molecular Genetics · doi:10.1093/hmg/6.9.1535 · Cited by 128 · see citing works
Amyloid β‐proteins 1—40 and 1—42(43) in the soluble fraction of extra‐ and intracranial blood vessels
Shinkai, Y., Yoshimura, M., Ito, Y., Odaka, A., Suzuki, N., Yanagisawa, K., & Ihara, Y. (1995) · Annals of Neurology · doi:10.1002/ana.410380312 · Cited by 127 · see citing works
γ-secretase modulators and presenilin 1 mutants act differently on presenilin/γ-secretase function to cleave Aβ42 and Aβ43
Okochi, M., Tagami, S., Yanagida, K., Takami, M., Kodama, T. S., Mori, K., Nakayama, T., Ihara, Y., & Takeda, M. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.11.028 · Cited by 123 · see citing works
Rodent Aβ Modulates the Solubility and Distribution of Amyloid Deposits in Transgenic Mice
Jankowsky, J. L., Younkin, L. H., Gonzales, V., Fadale, D. J., Slunt, H. H., Lester, H. A., Younkin, S. G., & Borchelt, D. R. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m611050200 · Cited by 122 · see citing works
Self-citation
Effect of Apolipoprotein E Allele ε4 on the Initial Phase of Amyloid β-Protein Accumulation in the Human Brain
Morishima-Kawashima, M., Oshima, N., Ogata, H., Yamaguchi, H., Yoshimura, M., Sugihara, S., & Ihara, Y. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64847-x · Cited by 119 · see citing works
Safety, tolerability and immunogenicity of an active anti-Aβ40 vaccine (ABvac40) in patients with Alzheimer’s disease: a randomised, double-blind, placebo-controlled, phase I trial
Lacosta, A.-M., Pascual-Lucas, M., Pesini, P., Casabona, D., Pérez-Grijalba, V., Marcos-Campos, I., Sarasa, L., Canudas, J., Badi, H., Monleón, I., et al. (2018) · Alzheimer's Research & Therapy · doi:10.1186/s13195-018-0340-8 · Cited by 111 · see citing works
Appearance of Sodium Dodecyl Sulfate-Stable Amyloid β-Protein (Aβ) Dimer in the Cortex During Aging
Enya, M., Morishima-Kawashima, M., Yoshimura, M., Shinkai, Y., Kusui, K., Khan, K., Games, D., Schenk, D., Sugihara, S., Yamaguchi, H., et al. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65273-x · Cited by 111 · see citing works
Intracellular Accumulation of Insoluble, Newly Synthesized Aβn-42 in Amyloid Precursor Protein-transfected Cells That Have Been Treated with Aβ1–42
Yang, A. J., Chandswangbhuvana, D., Shu, T., Henschen, A., & Glabe, C. G. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.29.20650 · Cited by 108 · see citing works
Amyloid‐β protein (Aβ) Glu11 is the major β‐secretase site of β‐site amyloid‐β precursor protein‐cleaving enzyme 1(BACE1), and shifting the cleavage site to Aβ Asp1 contributes to Alzheimer pathogenesis
Deng, Y., Wang, Z., Wang, R., Zhang, X., Zhang, S., Wu, Y., Staufenbiel, M., Cai, F., & Song, W. (2013) · European Journal of Neuroscience · doi:10.1111/ejn.12235 · Cited by 108 · see citing works
Additive Effects of PS1 and APP Mutations on Secretion of the 42-Residue Amyloid β-Protein
Citron, M., Eckman, C. B., Diehl, T. S., Corcoran, C., Ostaszewski, B. L., Xia, W., Levesque, G., St. George Hyslop, P., Younkin, S. G., & Selkoe, D. J. (1998) · Neurobiology of Disease · doi:10.1006/nbdi.1998.0183 · Cited by 101 · see citing works
Self-citation
The impact of Aβ-plaques on cortical cholinergic and non-cholinergic presynaptic boutons in alzheimer's disease-like transgenic mice
Hu, L., Wong, T. P., Côté, S. L., Bell, K. F. S., & Cuello, A. C. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00394-4 · Cited by 90 · see citing works

Authors: Suzuki, N., Cheung, T. T., Cai, X.-D., Odaka, A., Otvos, L., Eckman, C., Golde, T. E., & Younkin, S. G.
Affiliations: Takeda (Japan) (JP)
Case Western Reserve University (US)
Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
ORCID: Suzuki, Nobuhiro
Golde, Todd E.
Younkin, Steven G.
Venue: Science
Publisher: American Association for the Advancement of Science (AAAS)
Published: 1994-05-27
Volume: 264
Issue: 5163
Pages: 1336-1340
ISSN: 0036-8075 (ISSN-L)
1095-9203
DOI: 10.1126/science.8191290
OpenAlex: W1980906872
Cited by: 1,471
References: 6
Citations by year: 2026: 8 · 2025: 18 · 2024: 23 · 2023: 19 · 2022: 27 · 2021: 12 · 2020: 28 · 2019: 23 · 2018: 27 · 2017: 27 · 2016: 23 · 2015: 27 · 2014: 27 · 2013: 33 · 2012: 45
FWCI: 67.37
Type: journal article
Language: en
Open access: closed
Locations: Science (publishedVersion)
PubMed (publishedVersion)
Funders: National Institute on Aging (AG06656, R01AG006656)
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: amyloid-beta, amyloid precursor protein, familial Alzheimer's disease, amyloid fibril formation, amyloid deposition, carboxyl-terminal peptide, neuroblastoma cells
MeSH terms: Alzheimer Disease, Enzyme-Linked Immunosorbent Assay, Humans, Mutation, Neuroblastoma, Transfection, Tumor Cells, Cultured, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Culture Media, Conditioned

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

An Increased Percentage of Long Amyloid β Protein Secreted by Familial Amyloid β Protein Precursor (βApp 717 ) Mutants

Abstract

Integrity signals

Claims the paper makes

Claims other papers make about this one

Cites

Cited by

Record

About these checks