The DOI matches its Crossref record; 29 of the 29 references it cites were found in a registry or an index.
Additive Effects of PS1 and APP Mutations on Secretion of the 42-Residue Amyloid β-Protein
Open accessAbstract
Humans harboring missense mutations in the presenilin 1 (PS1) gene undergo progressive cerebral deposition of the 42-residue amyloid beta-protein (A beta 42) at an early age and develop severe Alzheimer's disease. A beta 42 is selectively elevated in the conditioned media of cells expressing mutant but not wild-type PS1, indicating that presenilin mutations alter APP processing. Here we analyze the effects of various PS1 mutant constructs on the cellular production of A beta 42. A construct expressing only the PS1 N-terminal endoproteolytic fragment with the mutation Y115H causes no significant increase in A beta 42, whereas a full-length PS1 construct with the same mutation does. This result suggests that the pathogenic effect of mutant presenilins is produced by the full-length molecule even though only a minor proportion of total PS1 occurs as holoprotein in tissues and cell lines. We demonstrate that the effects of two different PS1 mutations are additive when engineered into the same PS1 molecule. Therefore, two mutations alter gamma-secretase processing of APP more than one and the PS1 mutations described to date do not cause the maximum possible PS1-mediated rise in A beta 42. When a PS1 mutation was expressed in cells carrying the APPV717I mutation, A beta 42 rose dramatically to become the predominant secreted A beta species, an observation of interest for transgenic modeling of AD. Our results are consistent with the hypothesis that presenilin is a major regulator of the proteolytic processing of APP by gamma-secretases.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
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?
In the citing paper
“Moreover, the intermolecular combination of A 𝛃 42 -elevating mutations in APP and PS1 also additively increased A 𝛃 42 production (Citron et al., 1998).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Citron et al., 1998
In the citing paper
“In particular, the intramolecular combination of I716V and V717I mutations within APP doubled A 𝛃 42 production compared with the individual mutations (Eckman et al., 1997), as did the two PS1 FAD mutations M146L and L286V when introduced together into PS1 (Citron et al., 1998).”
From Intraneuronal β-Amyloid Aggregates, Neurodegeneration, and Neuron Loss in Transgenic Mice with Five Familial Alzheimer's Disease Mutations: Potential Factors in Amyloid Plaque Formation (2006) · cites this paper as Citron et al., 1998
In the citing paper
“The 5XFAD mouse, along with the APPSLPS1KI, is one of a few known mouse models that exhibits significant neuron loss in addition to displaying other AD hallmarks such as amyloid plaques [10,11,16].”
From Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation (2013) · cites this paper as [11]
In the citing paper
“Frank neuron loss has been observed in two aggressive amyloid plaque transgenic mouse models that also exhibit accumulation of intraneuronal Aβ42 prior to plaque formation: the 5XFAD and APPSLPS1K1 lines [10,11].”
From Neuron loss in the 5XFAD mouse model of Alzheimer’s disease correlates with intraneuronal Aβ42 accumulation and Caspase-3 activation (2013) · cites this paper as [11]
Citations
Cites
Cloning of a gene bearing missense mutations in early-onset familial Alzheimer's disease
Sherrington, R., Rogaev, E. I., Liang, Y., Rogaeva, E. A., Levesque, G., Ikeda, M., Chi, H., Lin, C., Li, G., Holman, K., et al. (1995) · Nature · doi:10.1038/375754a0 · Cited by 4,051
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
Self-citationIsolation and quantification of soluble Alzheimer's β-peptide from biological fluids
Seubert, P., Vigo-Pelfrey, C., Esch, F., Lee, M., Dovey, H., Davis, D., Sinha, S., Schiossmacher, M., Whaley, J., Swindlehurst, C., et al. (1992) · Nature · doi:10.1038/359325a0 · Cited by 1,731
Self-citationIncreased amyloid-β42(43) in brains of mice expressing mutant presenilin 1
Duff, K., Eckman, C., Zehr, C., Yu, X., Prada, C.-M., Pérez‐Tur, J., Hutton, M., Buée, L., Harigaya, Y., Yager, D., et al. (1996) · Nature · doi:10.1038/383710a0 · Cited by 1,486
Self-citationBorchelt, 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
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
Self-citationAmyloid, the presenilins and Alzheimer’s disease
Hardy, J. (1997) · Trends in Neurosciences · doi:10.1016/s0166-2236(96)01030-2 · Cited by 1,370
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
Self-citationEndoproteolysis of Presenilin 1 and Accumulation of Processed Derivatives In Vivo
Thinakaran, G., Borchelt, D., Lee, M. K., Slunt, H. H., Spitzer, L., Kim, G. J., Ratovitski, T., Davenport, F., Nordstedt, C., Seeger, M., et al. (1996) · Neuron · doi:10.1016/s0896-6273(00)80291-3 · Cited by 1,025
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
Kovacs, D. M., Fausett, H. J., Page, K. J., Kim, T., Moir, R. D., Merriam, D. E., Hollister, R. D., Hallmark, O. G., Mancini, R., Felsenstein, K. M., et al. (1996) · Nature Medicine · doi:10.1038/nm0296-224 · Cited by 552
(1997) · doi:10.1073/pnas.94.4.1550 · Cited by 535
Lemere, C. A., Lopera, F., Kosik, K. S., Lendon, C. L., Ossa, J., Saido, T. C., Yamaguchi, H., Ruiz, A., Martinez, A., Madrigal, L., et al. (1996) · Nature Medicine · doi:10.1038/nm1096-1146 · Cited by 487
Self-citationClark, R. F., Hutton, M., Fuldner, M., Froelich, S., Karran, E., Talbot, C., Crook, R., Lendon, C., Prihar, G., He, C., et al. (1995) · Nature Genetics · doi:10.1038/ng1095-219 · Cited by 474
Lopera, F. (1997) · JAMA: The Journal of the American Medical Association · doi:10.1001/jama.1997.03540340027028 · Cited by 351
Evidence that Aβ42 is the real culprit in alzheimer's disease
Younkin, S. G. (1995) · Annals of Neurology · doi:10.1002/ana.410370303 · Cited by 331
Self-citationThinakaran, G., Harris, C. L., Ratovitski, T., Davenport, F., Slunt, H. H., Price, D. L., Borchelt, D., & Sisodia, S. S. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.45.28415 · Cited by 316
Podlisny, M. B., Citron, M., Amarante, P., Sherrington, R., Xia, W., Zhang, J., Diehl, T. S., Levesque, G., Fraser, P., Haass, C., et al. (1997) · Neurobiology of Disease · doi:10.1006/nbdi.1997.0129 · Cited by 296
Self-citationCitron, 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
Self-citationXia, W., Zhang, J., Kholodenko, D., Citron, M., Podlisny, M. B., Teplow, D. B., Haass, C., Seubert, P. A., Koo, E. H., & Selkoe, D. J. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.12.7977 · Cited by 286
Self-citationA mutation in Alzheimerʼs disease destroying a splice acceptor site in the presenilin-1 gene
Pérez‐Tur, J., Froelich, S., Prihar, G., Crook, R., Baker, M., Duff, K., Wragg, M. A., Busfield, F., Lendon, C. L., Clark, R. F., et al. (1995) · Neuroreport · doi:10.1097/00001756-199512000-00071 · Cited by 264
Lopera, F. J. (1997) · JAMA · doi:10.1001/jama.277.10.793 · Cited by 255
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 229
Self-citationEndoproteolytic Processing and Stabilization of Wild-type and Mutant Presenilin
Ratovitski, T., Slunt, H. H., Thinakaran, G., Price, D. L., Sisodia, S. S., & Borchelt, D. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.39.24536 · Cited by 208
Hyperaccumulation of FAD-linked presenilin 1 variants in vivo
Lee, M. K., Borchelt, D., Kim, G. J., Thinakaran, G., Slunt, H. H., Ratovitski, T., Martin, L. J., Kittur, A., Gandy, S., Levey, A. I., et al. (1997) · Nature Medicine · doi:10.1038/nm0797-756 · Cited by 148
Mercken, M. H., Takahashi, H., Honda, T., Sato, K., Murayama, M., Nakazato, Y., Noguchi, K., Imahori, K., & Takashima, A. (1996) · FEBS Letters · doi:10.1016/0014-5793(96)00608-4 · Cited by 124
Increased Aβ42(43) from cell lines expressing presenilin 1 mutations
Mehta, N. D., Refolo, L. M., Eckman, C., Sanders, S., Yager, D., Perez‐Tur, J., Younkin, S., Duff, K., Hardy, J., & Hutton, M. (1998) · Annals of Neurology · doi:10.1002/ana.410430217 · Cited by 101
Self-citationInhibition of Amyloid β-Protein Production in Neural Cells by the Serine Protease Inhibitor AEBSF
Citron, M., Diehl, T. S., Capell, A., Haass, C., Teplow, D. B., & Selkoe, D. J. (1996) · Neuron · doi:10.1016/s0896-6273(00)80290-1 · Cited by 89
Self-citation
Flagged first, then by citations
Research works printed but not linked: 1
- Zhang, 1997, Subcellular distribution of presenilin in transfected cells, Soc. Neurosci. Abstr.
Cited by
Sorted by citations
Oakley, H., Cole, S. L., Logan, S., Maus, E., Shao, P., Craft, J., Guillozet-Bongaarts, A., Ohno, M., Disterhoft, J., Van Eldik, L., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.1202-06.2006 · Cited by 3,530
“…the reports that intramolecular combination of FAD mutations in either APP or PS1 act additively to increase A 42 generation (Eckman et al., 1997; Citron et al., 1998), we established transgenic mouse lines that co-overexpress human APP695 with the Swedish (K670N, M671L), Florida (I716V), and…”
BackgroundChishti, 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
Self-citationNicastrin modulates presenilin-mediated notch/glp-1 signal transduction and βAPP processing
Yu, G., Nishimura, M., Arawaka, S., Levitan, D. J., Zhang, L., Tandon, A., Song, Y., Rogaeva, E. A., Chen, F., Kawarai, T., et al. (2000) · Nature · doi:10.1038/35024009 · Cited by 929
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
Eimer, W. A., & Vassar, R. (2013) · Molecular Neurodegeneration · doi:10.1186/1750-1326-8-2 · Cited by 425
“In the case of the 5XFAD model, the mouse overexpresses APP with K670N/M671L (Swedish mutation [12]), I716V (Florida mutation [13]), and V717I (London mutation [14]), and PS1 with M146L and L286V mutations [15].”
Background
Metadata
- Authors
- 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.
- Affiliations
- Amgen (United States) (US)
- Mayo Clinic (US)
- Harvard University (US)
- Venue
- Neurobiology of Disease
- Publisher
- Elsevier BV
- Published
- 1998-08
- Volume
- 5
- Issue
- 2
- Pages
- 107-116
- ISSN
- 0969-9961 (ISSN-L)
- OpenAlex
- W2012968591
- Cited by
- 101
- References
- 28
- Citations by year
- 2026: 3 · 2024: 1 · 2023: 1 · 2022: 3 · 2021: 1 · 2020: 3 · 2019: 5 · 2018: 4 · 2017: 3 · 2016: 2 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 2
- FWCI
- 5.67
- Type
- journal article
- Language
- en
- Open access
- green
- doaj.org
- Licence
- Locations
- Neurobiology of Disease (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health
- National Institute on Aging (AG 12749, AG-06173, R01AG012749)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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
- presenilin 1, APP mutations, amyloid-beta 42, gamma-secretase, APP processing, Alzheimer's disease, conditioned medium, transgenic mouse model
- MeSH terms
- Alzheimer Disease, Cell Line, Gene Expression Regulation, Humans, Leucine, Membrane Proteins, Methionine, Peptide Fragments, Valine, Amyloid beta-Peptides, Mutagenesis, Site-Directed, Amyloid beta-Protein Precursor, Age of Onset, Amino Acid Substitution, Presenilin-1
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
