Bioluminescence imaging of Aβ deposition in bigenic mouse models of Alzheimer's disease
Open accessAbstract
Transgenic (Tg) mouse models of Alzheimer's disease have served as valuable tools for investigating pathogenic mechanisms related to Aβ accumulation. However, assessing disease status in these animals has required time-consuming behavioral assessments or postmortem neuropathological analysis. Here, we report a method for tracking the progression of Aβ accumulation in vivo using bioluminescence imaging (BLI) on two lines of Tg mice, which express luciferase (luc) under control of the Gfap promoter as well as mutant human amyloid precursor protein. Bigenic mice exhibited an age-dependent increase in BLI signals that correlated with the deposition of Aβ in the brain. Bioluminescence signals began to increase in 7-mo-old Tg(CRND8: Gfap -luc) mice and 14-mo-old Tg(APP23: Gfap -luc) mice. When Tg(APP23: Gfap -luc) mice were inoculated with brain homogenates from aged Tg(APP23) mice, BLI detected the accelerated disease onset and induced Aβ deposition at 11 mo of age. Because of its rapid, noninvasive, and quantitative format, BLI permits the objective repeated analysis of individual mice at multiple time points, which is likely to facilitate the testing of Aβ-directed therapeutics.
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?
Cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds.
“Experimentally, cerebral β-amyloidosis can be exogenously induced by exposure to dilute brain extracts containing aggregated Aβ seeds.”
From Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders (2011) · cites this paper as [53]
Cites
1 retracted
RETRACTED ARTICLE: A specific amyloid-β protein assembly in the brain impairs memory
Lesné, S., Koh, M. T., Kotilinek, L., Kayed, R., Glabe, C. G., Yang, A., Gallagher, M., & Ashe, K. H. (2006) · Nature · doi:10.1038/nature04533 · Cited by 2,769 · see citing works
RetractedThe 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
Developments of a water-maze procedure for studying spatial learning in the rat
Morris, R. (1984) · Journal of Neuroscience Methods · doi:10.1016/0165-0270(84)90007-4 · Cited by 7,180 · see citing works
Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B
Klunk, W. E., Engler, H., Nordberg, A., Wang, Y., Blomqvist, G., Holt, D. P., Bergström, M., Savitcheva, I., Huang, G., Estrada, S., et al. (2004) · Annals of Neurology · doi:10.1002/ana.20009 · Cited by 4,496 · see citing works
Walsh, D. M., Klyubin, I., Fadeeva, J. V., Cullen, W. K., Anwyl, R., Wolfe, M. S., Rowan, M. J., & Selkoe, D. J. (2002) · Nature · doi:10.1038/416535a · Cited by 4,291 · 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
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
Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17
Hutton, M., Lendon, C. L., Rizzu, P., Baker, M., Froelich, S., Houlden, H., Pickering-Brown, S., Chakraverty, S., Isaacs, A., Grover, A., et al. (1998) · Nature · doi:10.1038/31508 · Cited by 3,498 · see citing works
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
Synapse Loss and Microglial Activation Precede Tangles in a P301S Tauopathy Mouse Model
Yoshiyama, Y., Higuchi, M., Zhang, B., Huang, S.-M., Iwata, N., Saido, T. C., Maeda, J., Suhara, T., Trojanowski, J. Q., & Lee, V. M.-Y. (2007) · Neuron · doi:10.1016/j.neuron.2007.01.010 · Cited by 2,208 · see citing works
Mucke, L., Masliah, E., Yu, G.-Q., Mallory, M., Rockenstein, E. M., Tatsuno, G., Hu, K., Kholodenko, D., Johnson-Wood, K., & McConlogue, L. (2000) · The Journal of Neuroscience · doi:10.1523/jneurosci.20-11-04050.2000 · Cited by 1,856 · see citing works
Transmission and spreading of tauopathy in transgenic mouse brain
Clavaguera, F., Bolmont, T., Crowther, R. A., Abramowski, D., Frank, S., Probst, A., Fraser, G., Stalder, A. K., Beibel, M., Staufenbiel, M., et al. (2009) · Nature Cell Biology · doi:10.1038/ncb1901 · Cited by 1,803 · see citing works
Brain interleukin 1 and S-100 immunoreactivity are elevated in Down syndrome and Alzheimer disease.
Griffin, W. S., Stanley, L. C., Ling, C., White, L., MacLeod, V, Perrot, L. J., White, C. L., & Araoz, C. (1989) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.86.19.7611 · Cited by 1,777 · see citing works
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
Mutation in the tau gene in familial multiple system tauopathy with presenile dementia
Spillantini, M. G., Murrell, J. R., Goedert, M., Farlow, M. R., Klug, A., & Ghetti, B. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.13.7737 · Cited by 1,474 · see citing works
Aβ peptide immunization reduces behavioural impairment and plaques in a model of Alzheimer's disease
Janus, C., Pearson, J., McLaurin, J., Mathews, P. M., Jiang, Y., Schmidt, S. D., Chishti, M. A., Horne, P., Heslin, D., French, J., et al. (2000) · Nature · doi:10.1038/35050110 · Cited by 1,431 · see citing works
Tau is a candidate gene for chromosome 17 frontotemporal dementia
Poorkaj, P., Bird, T. D., Wijsman, E., Nemens, E., Garruto, R. M., Anderson, L., Andreadis, A., Wiederholt, W. C., Raskind, M., & Schellenberg, G. D. (1998) · Annals of Neurology · doi:10.1002/ana.410430617 · Cited by 1,374 · see citing works
Neuronal α-Synucleinopathy with Severe Movement Disorder in Mice Expressing A53T Human α-Synuclein
Giasson, B. I., Duda, J. E., Quinn, S. M., Zhang, B., Trojanowski, J. Q., & Lee, V. M.-Y. (2002) · Neuron · doi:10.1016/s0896-6273(02)00682-7 · Cited by 1,266 · see citing works
Rovelet‐Lecrux, A., Hannequin, D., Raux, G., Meur, N. L., Laquerrière, A., Vital, A., Dumanchin‐Njock, C., Feuillette, S., Brice, A., Vercelletto, M., et al. (2005) · Nature Genetics · doi:10.1038/ng1718 · Cited by 1,249 · see citing works
Rapid appearance and local toxicity of amyloid-β plaques in a mouse model of Alzheimer’s disease
Meyer-Luehmann, M., Spires-Jones, T. L., Prada, C., Garcia-Alloza, M., de Calignon, A., Rozkalne, A., Koenigsknecht-Talboo, J., Holtzman, D. M., Bacskai, B. J., & Hyman, B. T. (2008) · Nature · doi:10.1038/nature06616 · Cited by 987 · see citing works
Exogenous Induction of Cerebral ß-Amyloidogenesis Is Governed by Agent and Host
Meyer-Luehmann, M., Coomaraswamy, J., Bolmont, T., Kaeser, S., Schaefer, C., Kilger, E., Neuenschwander, A., Abramowski, D., Frey, P., Jaton, A. L., et al. (2006) · Science · doi:10.1126/science.1131864 · Cited by 971 · see citing works
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
Allen, B., Ingram, E., Takao, M., Smith, M. J., Jakes, R., Virdee, K., Yoshida, H., Holzer, M., Craxton, M., Emson, P. C., et al. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-21-09340.2002 · Cited by 746 · see citing works
IRIZARRY, M. C., MCNAMARA, M., FEDORCHAK, K., HSIAO, K., & HYMAN, B. T. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199709000-00002 · Cited by 649 · see citing works
Strain and gender differences in the behavior of mouse lines commonly used in transgenic studies
Võikar, V., Kõks, S., Vasar, E., & Rauvala, H. (2001) · Physiology & Behavior · doi:10.1016/s0031-9384(00)00405-4 · Cited by 420 · see citing works
Klunk, W. E., Lopresti, B. J., Ikonomović, M. D., Lefterov, I. M., Koldamova, R. P., Abrahamson, E. E., Debnath, M. L., Holt, D. P., Huang, G.-F., Shao, L., et al. (2005) · Journal of Neuroscience · doi:10.1523/jneurosci.2990-05.2005 · Cited by 376 · see citing works
Owen, E. H., Logue, S. F., Rasmussen, D. L., & Wehner, J. M. (1997) · Neuroscience · doi:10.1016/s0306-4522(97)00165-6 · Cited by 347 · see citing works
Induction of cerebral β-amyloidosis: Intracerebral versus systemic Aβ inoculation
Eisele, Y. S., Bolmont, T., Heikenwalder, M., Langer, F., Jacobson, L. H., Yan, Z.-X., Roth, K., Aguzzi, A., Staufenbiel, M., Walker, L. C., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903200106 · Cited by 279 · see citing works
Amyloid β-Protein Dimers Rapidly Form Stable Synaptotoxic Protofibrils
O'Nuallain, B., Freir, D. B., Nicoll, A. J., Risse, E., Ferguson, N., Herron, C. E., Collinge, J., & Walsh, D. M. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.3537-10.2010 · Cited by 259 · see citing works
Alamed, J., Wilcock, D. M., Diamond, D. M., Gordon, M. N., & Morgan, D. (2006) · Nature Protocols · doi:10.1038/nprot.2006.275 · Cited by 256 · see citing works
Progressive age-related impairment of cognitive behavior in APP23 transgenic mice
Kelly, P. H., Bondolfi, L., Hunziker, D., Schlecht, H. P., Carver, K., Maguire, E., Abramowski, D., Wiederhold, K., Sturchler, C., Jucker, M., et al. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(02)00098-2 · Cited by 187 · see citing works
Syková, E., Voříšek, I., Antonova, T., Mazel, T., Meyer-Luehmann, M., Jucker, M., Hájek, M., Or, M., & Bureš, J. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408235102 · Cited by 121 · see citing works
Non-invasive imaging of GFAP expression after neuronal damage in mice
Zhu, L., Ramboz, S., Hewitt, D., Boring, L. F., Grass, D., & Purchio, A. F. (2004) · Neuroscience Letters · doi:10.1016/j.neulet.2004.06.020 · Cited by 102 · see citing works
Keller, A. F., Gravel, M., & Križ, J. (2008) · Glia · doi:10.1002/glia.20836 · Cited by 95 · see citing works
Age-progressing cognitive impairments and neuropathology in transgenic CRND8 mice
Hyde, L. A., Kazdoba, T. M., Grilli, M., Lozza, G., Brussa, R., Zhang, Q., Wong, G. T., McCool, M. F., Zhang, L., Parker, E. M., et al. (2005) · Behavioural Brain Research · doi:10.1016/j.bbr.2004.12.017 · Cited by 80 · see citing works
Okamura, N., Mori, M., Furumoto, S., et al. (2011) · Journal of Alzheimer s Disease · doi:10.3233/jad-2010-100270 · Cited by 60 · see citing works
Measuring prions by bioluminescence imaging
Tamgüney, G., Francis, K. P., Giles, K., Lemus, A., DeArmond, S. J., & Prusiner, S. B. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0907339106 · Cited by 60 · see citing works
Self-citationCould They All Be Prion Diseases?
Miller, G. (2009) · Science · doi:10.1126/science.326.5958.1337 · Cited by 48 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pathogenic protein seeding in Alzheimer disease and other neurodegenerative disorders
Jucker, M., & Walker, L. C. (2011) · Annals of Neurology · doi:10.1002/ana.22615 · Cited by 622 · see citing works
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455 · see citing works
Self-citationNeurodegenerative Diseases: Expanding the Prion Concept
Walker, L. C., & Jucker, M. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033828 · Cited by 361 · see citing works
Soluble Aβ Seeds Are Potent Inducers of Cerebral β-Amyloid Deposition
Langer, F., Eisele, Y. S., Fritschi, S. K., Staufenbiel, M., Walker, L. C., & Jucker, M. (2011) · The Journal of Neuroscience · doi:10.1523/jneurosci.3088-11.2011 · Cited by 237 · see citing works
Imaging of cerebrovascular pathology in animal models of Alzheimer's disease
Klohs, J., Rudin, M., Shimshek, D. R., & Beckmann, N. (2014) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2014.00032 · Cited by 82 · see citing works
Jin, P., Kim, J.-A., Choi, D.-Y., Lee, Y.-J., Jung, H. S., & Hong, J. T. (2013) · Journal of Neuroinflammation · doi:10.1186/1742-2094-10-2 · Cited by 59 · see citing works
Johnson, N. R., Yuan, P., Castillo, E., Lopez, T. P., Yue, W., Bond, A., Rivera, B. M., Sullivan, M. C., Hirouchi, M., Giles, K., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35753-w · Cited by 46 · see citing works
Comparative pathobiology of β-amyloid and the unique susceptibility of humans to Alzheimer's disease
Rosen, R. F., Tomidokoro, Y., Farberg, A. S., Dooyema, J., Ciliax, B., Preuss, T. M., Neubert, T. A., Ghiso, J. A., LeVine, H., & Walker, L. C. (2016) · Neurobiology of Aging · doi:10.1016/j.neurobiolaging.2016.04.019 · Cited by 46 · see citing works
- Authors
- Watts, J. C., Giles, K., Grillo, S. K., Lemus, A., DeArmond, S. J., & Prusiner, S. B.
- Affiliations
- Institute for Neurodegenerative Diseases and
- Institute for Neurodegenerative Diseases (US)
- University of California, San Francisco (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2011-01-24
- Volume
- 108
- Issue
- 6
- Pages
- 2528-2533
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC3038719
- OpenAlex
- W2133007412
- Cited by
- 109
- References
- 38
- Citations by year
- 2026: 1 · 2025: 1 · 2023: 7 · 2022: 4 · 2021: 9 · 2020: 7 · 2019: 7 · 2018: 4 · 2017: 2 · 2016: 10 · 2015: 8 · 2014: 19 · 2013: 15 · 2012: 8
- FWCI
- 10.69
- Type
- journal article
- Language
- en
- Update notices
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Larry L. Hillblom Foundation
- Lincy Foundation
- Sherman Fairchild Foundation
- National Institutes of Health
- Canadian Institutes of Health Research
- National Institute on Aging (AG010770, P01AG002132, P01AG021601, P01AG010770, AG002132, AG 021601, R37AG031220)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › bioluminescence and chemiluminescence research
- Keywords
- Alzheimer's disease, amyloid-beta deposition, bioluminescence imaging, transgenic mouse model, APP23 mice, non-invasive imaging
- MeSH terms
- Aging, Alzheimer Disease, Animals, Diagnostic Imaging, Disease Models, Animal, Glial Fibrillary Acidic Protein, Humans, Luciferases, Mice, Transgenic, Nerve Tissue Proteins, Promoter Regions, Genetic, Amyloid beta-Protein Precursor, Luminescence, Mice
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