The DOI matches its Crossref record; 40 of the 40 references it cites were found in a registry or an index.
Familial Alzheimer's Disease–Linked Presenilin 1 Variants Elevate Aβ1–42/1–40 Ratio In Vitro and In Vivo
Open accessAbstract
Mutations in the presenilin 1 (PS1) and presenilin 2 genes cosegregate with the majority of early-onset familial Alzheimer's disease (FAD) pedigrees. We now document that the Abeta1-42(43)/Abeta1-40 ratio in the conditioned media of independent N2a cell lines expressing three FAD-linked PS1 variants is uniformly elevated relative to cells expressing similar levels of wild-type PS1. Similarly, the Abeta1-42(43)/Abeta1-40 ratio is elevated in the brains of young transgenic animals coexpressing a chimeric amyloid precursor protein (APP) and an FAD-linked PS1 variant compared with brains of transgenic mice expressing APP alone or transgenic mice coexpressing wild-type human PS1 and APP. These studies provide compelling support for the view that one mechanism by which these mutant PS1 cause AD is by increasing the extracellular concentration of Abeta peptides terminating at 42(43), species that foster Abeta deposition.
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
“each of these genetic forms of AD either selectively increases the extracellular concentration of A42 (Suzuki et al., 1994;Borchelt et al., 1996;Duff et al., 1996;Scheuner et al., 1996;Citron et al., 1997) or increases both A42 and A40 (Cai et al., 1993;Citron et al., 1994;Scheuner et al., 1996).”
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 Borchelt et al., 1996
In the citing paper
“In FAD, metabolic effects of mutations promote increased levels of total Aβ, or increased Aβ42 to Aβ40 ratio (Borchelt et al., 1996; Citron et al., 1992), conditions that favor oligomerization.”
From The Aβ oligomer hypothesis for synapse failure and memory loss in Alzheimer’s disease (2011) · cites this paper as Borchelt et al., 1996
Citations
Cites
1 retracted
Familial Alzheimer's disease associated with S182 codon 286 mutation
Chapman, J., Asherov, A., Wang, N., Treves, T. A., Korczyn, A. D., & Goldfarb, L. G. (1995) · The Lancet · doi:10.1016/s0140-6736(95)91723-3 · Cited by 25
RetractedGoate, A., Chartier-Harlin, M.-C., Mullan, M., Brown, J., Crawford, F., Fidani, L., Giuffra, L., Haynes, A., Irving, N., James, L., et al. (1991) · Nature · doi:10.1038/349704a0 · Cited by 4,659
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-citationCandidate gene for the chromosome 1 familial Alzheimer’s disease locus
Levy-Lahad, E., Wasco, W., Poorkaj, P., Romano, D. M., Oshima, J., Pettingell, W. H., Yu, C.-E., Jondro, P. D., Schmidt, S. D., Wang, K., et al. (1995) · Science · doi:10.1126/science.7638622 · Cited by 2,577
Jarrett, J. T., & Lansbury, P. T. (1993) · Cell · doi:10.1016/0092-8674(93)90635-4 · Cited by 2,178
Rogaev, E. I., Sherrington, R., Rogaeva, E. A., Levesque, G., Ikeda, M., Liang, Y., Chi, H., Lin, C., Holman, K., Tsuda, T., et al. (1995) · Nature · doi:10.1038/376775a0 · Cited by 2,052
Jarrett, J. T., Berger, E. P., & Lansbury, P. T. (1993) · Biochemistry · doi:10.1021/bi00069a001 · Cited by 2,022
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
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
Mullan, M., Crawford, F., Axelman, K., Houlden, H., Lilius, L., Winblad, B., & Lannfelt, L. (1992) · Nature Genetics · doi:10.1038/ng0892-345 · Cited by 1,513
Suzuki, 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-citationChartier-Harlin, M.-C., Crawford, F., Houlden, H., Warren, A., Hughes, D., Fidani, L., Goate, A., Rossor, M., Roques, P., Hardy, J., et al. (1991) · Nature · doi:10.1038/353844a0 · Cited by 1,214
Endoproteolysis 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
Self-citationAssembly 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
Genetic Linkage Evidence for a Familial Alzheimer's Disease Locus on Chromosome 14
Schellenberg, G. D., Bird, T. D., Wijsman, E. M., Orr, H. T., Anderson, L., Nemens, E. J., White, J. A., Bonnycastle, L. L., Weber, J. L., Alonso, M. E., et al. (1992) · Science · doi:10.1126/science.1411576 · Cited by 957
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
Self-citationA Familial Alzheimer's Disease Locus on Chromosome 1
Levy‐Lahad, E., Wijsman, E. M., Nemens, E. J., Anderson, L., Goddard, K. A. B., Weber, J. L., Bird, T. D., & Schellenberg, G. D. (1995) · Science · doi:10.1126/science.7638621 · Cited by 832
Roher, A. E., Lowenson, J. D., Clarke, S., Wolkow, C., Wang, R., Cotter, R. J., Reardon, I. M., Zürcher-Neely, H. A., Heinrikson, R. L., & Ball, M. J. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53661-9 · Cited by 799
Self-citationHendriks, L., van Duijn, C. M., Cras, P. P., Cruts, M., Hul, W. V., van Harskamp, F., Warren, A., McInnis, M. G., Antonarakis, S. E., Martin, J., et al. (1992) · Nature Genetics · doi:10.1038/ng0692-218 · Cited by 741
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 · cited 7×
“…APPswe transgenes alone; lanes 5 and 6, transgenic mice harboring APPswe and mutant human PS1 transgenes; lanes 7 and 8, transgenic mice harboring APPswe and wild-type human PS1 transgenes. sandwich ELISA assays, described above (Suzuki et al., 1994; Gravina et al., 1995; Scheuner et al., 1996).”
BackgroundMethodInfluentialSelf-citationLemere, C. A., Blusztajn, J. K., Yamaguchi, H., Wisniewski, T., Saido, T. C., & Selkoe, D. J. (1996) · Neurobiology of Disease · doi:10.1006/nbdi.1996.0003 · Cited by 584 · cited 3×
“…human APP alone (Figure 1B, lane 1) and z43 kDa and z27 kDa polypeptides, corresponding to full-(Iwatsubo et al., 1994; Gravina et al., 1995; Lemere et al., 1996a). length human PS1 and an N-terminal human PS1 derivative, respectively, in N2a lines stably expressing human wild-type PS1…”
BackgroundHsiao, K., Borchelt, D., Olson, K., Johannsdottir, R., Kitt, C. A., Yunis, W. S., Xu, S., Eckman, C., Younkin, S. G., Price, D., et al. (1995) · Neuron · doi:10.1016/0896-6273(95)90107-8 · Cited by 527
Self-citationLemere, 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
Clark, 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
Genetic evidence for a novel familial Alzheimer's disease locus on chromosome 14
George‐Hyslop, P. S., Haines, J. L., Rogaev, E. I., Mortilla, M., Vaula, G., Pericak‐Vance, M. A., Foncin, J. P., Montesi, M. P., Bruni, A. C., Sorbi, S., et al. (1992) · Nature Genetics · doi:10.1038/ng1292-330 · Cited by 467
Protease nexin-II, a potent anti-chymotrypsin, shows identity to amyloid β-protein precursor
Nostrand, W. E. V., Wagner, S. L., Suzuki, M., Choi, B. H., Farrow, J. S., Geddes, J. W., Cotman, C. W., & Cunningham, D. D. (1989) · Nature · doi:10.1038/341546a0 · Cited by 434
Amyloid β protein (Aβ) deposition: Aβ42(43) precedes Aβ40 in down Syndrome
Iwatsubo, T., Mann, D. M. A., Odaka, A., Suzuki, N., & Ihara, Y. (1995) · Annals of Neurology · doi:10.1002/ana.410370305 · Cited by 386
Sisodia, S., Koo, E., Hoffman, P., Perry, G. L., & Price, D. (1993) · Journal of Neuroscience · doi:10.1523/jneurosci.13-07-03136.1993 · Cited by 284
Self-citationNaruse, S., Igarashi, S., Aoki, K., Kaneko, K., Iihara, K., Miyatake, T., Kobayashi, H., Inuzuka, T., Shimizu, T., Kojima, T., et al. (1991) · The Lancet · doi:10.1016/0140-6736(91)91612-x · Cited by 281
Mutations of the presenilin I gene in families with early-onset Alzheimer's disease
Campion, D., Flaman, J., Brice, A., Hannequin, D., Dubois, B., Martin, C., Moreau, V., Charbonnier, F., Didierjean, O., Tardieu, S., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2373 · Cited by 277
A 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
Roses, A. D. (1994) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199409000-00002 · Cited by 252
Hyman, B. T., West, H. L., Rebeck, G. W., Buldyrev, S. V., Mantegna, R. N., Ukleja, M., Havlin, S., & Stanley, H. E. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.8.3586 · Cited by 212
Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3
Cruts, M., Backhovens, H., Wang, S., Gassen, G. V., Theuns, J., Jonghe, C. D., Wehnert, A., Voecht, J. D., Winter, G. D., Cras, P. P., et al. (1995) · Human Molecular Genetics · doi:10.1093/hmg/4.12.2363 · Cited by 180
Genetic dissection of Alzheimer disease, a heterogeneous disorder.
Schellenberg, G. D. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.19.8552 · Cited by 178
Familial Alzheimer's chromosome 14 mutations
Wasco, W., Pettingell, W. P., Jondro, P. D., Schmidt, S. D., Gurubhagavatula, S., Rodes, L., Di-Blasi, T., Romano, D., Guénette, S. Y., Kovacs, D. M., et al. (1995) · Nature Medicine · doi:10.1038/nm0995-848a · Cited by 109
Mutation analysis of presenilin 1 gene in Alzheimer's disease
Boteva, K., Vitek, M. P., Mitsuda, H., de Silva, H., Xu, P.-T., Small, G. W., & Gilbert, J. R. (1996) · The Lancet · doi:10.1016/s0140-6736(96)90261-5 · Cited by 57
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
Self-citationNucleotide sequence of the chromosome 14-encodedS182cDNA and revised secondary structure prediction
Slunt, H. H., Thinakaran, G., Lee, M. K., & Sisodia, S. S. (1995) · Amyloid · doi:10.3109/13506129509036925 · Cited by 31
Self-citation
Research works printed but not linked: 2
- Kim, 1988, Production and characterization of monoclonal antibodies reactive to synthetic cerebrovascular amyloid peptide, Neurosci. Res. Commun, 2, 121
- Kim, 1990, Detection and quantitation of amyloid B-peptide with 2 monoclonal antibodies, Neurosci. Res. Commun, 7, 113
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
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
“Previous studies have shown that mice coexpressing FAD mutant APP and PS1 transgenes exhibit additive increases in A 42 production (Borchelt et al., 1996, 1997; Citron et al., 1997; Holcomb et al., 1998), although rarely have more than two A 42-elevating FAD mutations been combined in transgenic…”
BackgroundImmunization 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
Self-citationThe molecular pathology of Alzheimer's disease
Selkoe, D. J. (1991) · Neuron · doi:10.1016/0896-6273(91)90052-2 · Cited by 2,708
Masters, C. L., Bateman, R., Blennow, K., Rowe, C. C., Sperling, R. A., & Cummings, J. L. (2015) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2015.56 · Cited by 1,853
Metadata
- Authors
- Borchelt, D. R., Thinakaran, G., Eckman, C. B., Lee, M. K., Davenport, F., Ratovitsky, T., Prada, C.-M., Kim, G., Seekins, S., Yager, D., Slunt, H. H., Wang, R., Seeger, M., Levey, A. I., Gandy, S. E., Copeland, N. G., Jenkins, N. A., Price, D. L., Younkin, S. G., & Sisodia, S. S.
- Affiliations
- Johns Hopkins University (US)
- Mayo Clinic in Florida (US)
- Rockefeller University (US)
- Cornell University (US)
- Emory University (US)
- Frederick National Laboratory for Cancer Research (US)
- Corresponding author
- Sisodia, Sangram S.
- ORCID
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 1996-11
- Volume
- 17
- Issue
- 5
- Pages
- 1005-1013
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2095745901
- Cited by
- 1,478
- References
- 40
- Citations by year
- 2026: 2 · 2025: 20 · 2024: 28 · 2023: 23 · 2022: 26 · 2021: 32 · 2020: 45 · 2019: 27 · 2018: 26 · 2017: 51 · 2016: 47 · 2015: 43 · 2014: 42 · 2013: 43 · 2012: 53
- FWCI
- 53.49
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Neuron (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG05689, P50AG005146, F32AG005689, AG 05146)
- National Institute of Neurological Disorders and Stroke (NS-20471)
- 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
- familial Alzheimer's disease, presenilin 1, PS1 mutations, amyloid-beta 42, amyloid precursor protein, transgenic mice, N2a cells, conditioned medium, amyloid deposition
- MeSH terms
- Alzheimer Disease, Animals, Brain Chemistry, Humans, Membrane Proteins, Mice, Transgenic, Mutation, Neuroblastoma, Recombinant Fusion Proteins, Transfection, Tumor Cells, Cultured, Gene Expression, Amyloid beta-Protein Precursor, Culture Media, Conditioned, Mice, 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
