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.
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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
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Research works printed but not linked: 1
- Zhang, 1997, Subcellular distribution of presenilin in transfected cells, Soc. Neurosci. Abstr.
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Items 101–103 of 103
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
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