Murine Aβ over-production produces diffuse and compact Alzheimer-type amyloid deposits
Open accessAbstract
INTRODUCTION: Transgenic overexpression of amyloid precursor protein (APP) genes that are either entirely human in sequence or have humanized Aβ sequences can produce Alzheimer-type amyloidosis in mice, provided the transgenes also encode mutations linked to familial Alzheimer's Disease (FAD). Although transgenic mice have been produced that overexpress wild-type mouse APP, no mice have been generated that express mouse APP with FAD mutations. Here we describe two different versions of such mice that produce amyloid deposits consisting of entirely of mouse Aβ peptides. One line of mice co-expresses mouse APP-Swedish (moAPPswe) with a human presenilin exon-9 deleted variant (PS1dE9) and another line expresses mouse APP-Swedish/Indiana (APPsi) using tetracycline-regulated vectors (tet.moAPPsi). RESULTS: Both lines of mice that produce mouse Aβ develop amyloid deposits, with the moAPPswe/PS1dE9 mice developing extracellular compact, cored, neuritic deposits that primarily localize to white matter tracts and meningial layers, whereas the tet.moAPPsi mice developed extracellular diffuse cortical/hippocampal deposits distributed throughout the parenchyma. CONCLUSIONS: These findings demonstrate that murine Aβ peptides have the capacity to produce amyloid deposits that are morphologically similar to deposits found in human AD provided the murine APP gene harbors mutations linked to human FAD.
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Sequence differences between mice and humans include 3 amino acids within the Aβ sequence (R5G, Y10F and H13R).
“Importantly, sequence differences between mice and humans include 3 amino acids within the Aβ sequence (R5G, Y10F and H13R)[155, 174].”
From Alzheimer's disease: experimental models and reality (2017) · cites this paper as [174]
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Cites
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
Amyloid oligomers exacerbate tau pathology in a mouse model of tauopathy
Selenica, M.-L. B., Brownlow, M., Jimenez, J. P., Lee, D. C., Pena, G., Dickey, C. A., Gordon, M. N., & Morgan, D. (2013) · Neurodegenerative Diseases · doi:10.1159/000337230 · Cited by 10,359 · see citing works
Amyloid plaque core protein in Alzheimer disease and Down syndrome.
Masters, C. L., Simms, G., Weinman, N. A., Multhaup, G., McDonald, B. L., & Beyreuther, K. (1985) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.82.12.4245 · Cited by 4,431 · 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
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
Alzheimer's disease and Down's syndrome: Sharing of a unique cerebrovascular amyloid fibril protein
Glenner, G. G., & Wong, C. W. (1984) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(84)91209-9 · Cited by 1,693 · see citing works
pEF-BOS, a powerful mammalian expression vector
Mizushima, S., & Nagata, S. (1990) · Nucleic Acids Research · doi:10.1093/nar/18.17.5322 · Cited by 1,632 · see citing works
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-citationControl of memory formation through regulated expression of a CaMKII transgene
Mayford, M., Bach, M. E., Huang, Y.-Y., Wang, L., Hawkins, R. D., & Kandel, E. R. (1996) · Science · doi:10.1126/science.274.5293.1678 · Cited by 1,550 · see citing works
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-citationSingle App knock-in mouse models of Alzheimer’s disease
Saito, T., Matsuba, Y., Mihira, N., Takano, J., Nilsson, P., Itohara, S., Iwata, N., & Saido, T. C. (2014) · Nature Neuroscience · doi:10.1038/nn.3697 · Cited by 1,447 · see citing works
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
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
Self-citationAtwood, C. S., Moir, R. D., Huang, X., Scarpa, R. C., Bacarra, N. M. E., Romano, D. M., Hartshorn, M. A., Tanzi, R. E., & Bush, A. I. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.21.12817 · Cited by 1,009 · see citing works
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 1,009 · see citing works
Self-citationA mouse model for Down syndrome exhibits learning and behaviour deficits
Reeves, R. H., Irving, N. G., Moran, T. H., Wohn, A., Kitt, C., Sisodia, S. S., Schmidt, C., Bronson, R. T., & Davisson, M. T. (1995) · Nature Genetics · doi:10.1038/ng1095-177 · Cited by 913 · see citing works
Co-expression of multiple transgenes in mouse CNS: a comparison of strategies
Jankowsky, J. L., Slunt, H. H., Ratovitski, T., Jenkins, N. A., Copeland, N. G., & Borchelt, D. (2001) · Biomolecular Engineering · doi:10.1016/s1389-0344(01)00067-3 · Cited by 819 · see citing works
Self-citationBACE1 is the major β-secretase for generation of Aβ peptides by neurons
Cai, H., Wang, Y.-S., McCarthy, D., Wen, H., Borchelt, D., Price, D. L., & Wong, P. (2001) · Nature Neuroscience · doi:10.1038/85064 · Cited by 791 · see citing works
Self-citationCu(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
An overview of APP processing enzymes and products.
Chow, V. W., Mattson, M. P., Wong, P. C., & Gleichmann, M. (2010) · NeuroMolecular Medicine · doi:10.1007/s12017-009-8104-z · Cited by 684 · see citing works
Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice
McGowan, E., Pickford, F., Kim, J., Onstead, L., Eriksen, J., Yu, C., Skipper, L., Murphy, M. P., Beard, J., Das, P., et al. (2005) · Neuron · doi:10.1016/j.neuron.2005.06.030 · Cited by 565 · see citing works
Self-citationEnvironmental Enrichment Mitigates Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Jankowsky, J. L., Melnikova, T., Fadale, D. J., Xu, G. M., Slunt, H. H., Gonzales, V., Younkin, L. H., Younkin, S. G., Borchelt, D. R., & Savonenko, A. V. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.5080-04.2005 · Cited by 517 · see citing works
Self-citationGuo, Q., Fu, W., Sopher, B. L., Miller, M. W., Ware, C. B., Martin, G. M., & Mattson, M. P. (1999) · Nature Medicine · doi:10.1038/4789 · Cited by 489 · see citing works
Conservation of brain amyloid proteins in aged mammals and humans with Alzheimer's disease.
Selkoe, D. J., Bell, D., Podlisny, M., Price, D. L., & Cork, L. (1987) · Science · doi:10.1126/science.3544219 · Cited by 471 · see citing works
A vector for expressing foreign genes in the brains and hearts of transgenic mice
Borchelt, D., Davis, J. A., Fischer, M., Lee, M. K., Slunt, H. H., Ratovitski, T., Regard, J. B., Copeland, N. G., Jenkins, N. A., Sisodia, S. S., et al. (1996) · Genetic Analysis Biomolecular Engineering · doi:10.1016/s1050-3862(96)00167-2 · Cited by 362 · see citing works
Self-citationCrook, R., Verkkoniemi, A., Pérez‐Tur, J., Mehta, N. D., Baker, M. C., Houlden, H., Farrer, M. J., Hutton, M., Lincoln, S., Hardy, J., et al. (1998) · Nature Medicine · doi:10.1038/nm0498-452 · Cited by 347 · see citing works
Yamamoto, T., & Hirano, A. (1986) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1986.tb00677.x · Cited by 330 · see citing works
Pardo, C. A., Xu, Z., Borchelt, D., Price, D. L., Sisodia, S. S., & Cleveland, D. W. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.4.954 · Cited by 314 · see citing works
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 313 · see citing works
Self-citationBiochemistry of altered brain proteins in Alzheimer's disease.
Selkoe, D. (1989) · Annual Review of Neuroscience · doi:10.1146/annurev.ne.12.030189.002335 · Cited by 261 · see citing works
Fraser, P. E., Nguyen, J. T., Inouye, H., Surewicz, W. K., Selkoe, D. J., Podlisny, M. B., & Kirschner, D. A. (1992) · Biochemistry · doi:10.1021/bi00159a011 · Cited by 248 · see citing works
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-citationPresenilin-1 Knockin Mice Reveal Loss-of-Function Mechanism for Familial Alzheimer’s Disease
Xia, D., Watanabe, H., Wu, B., Lee, S. H., Li, Y., Tsvetkov, E., Bolshakov, V. Y., Shen, J., & Kelleher, R. J. (2015) · Neuron · doi:10.1016/j.neuron.2015.02.010 · Cited by 226 · see citing works
β-Amyloid precursor polypeptide in SAMP8 mice affects learning and memory
Morley, J. E., Kumar, V. B., Bernardo, A. E., Farr, S. A., Uezu, K., Tumosa, N., & Flood, J. F. (2000) · Peptides · doi:10.1016/s0196-9781(00)00342-9 · Cited by 219 · see citing works
Vallet, P. G., Guntern, R., Hof, P. R., Golaz, J., Delacourte, A., Robakis, N. K. R. K., & Bouras, C. (1992) · Acta Neuropathologica · doi:10.1007/bf00308476 · Cited by 170 · see citing works
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 145 · see citing works
Self-citationGuntern, R., Bouras, C., Hof, P. R., & Vallet, P. G. (1992) · Cellular and Molecular Life Sciences · doi:10.1007/bf01923594 · Cited by 135 · see citing works
Cheng, X., Zhou, W., & Zhang, Y. (2013) · Ageing Research Reviews · doi:10.1016/j.arr.2013.10.002 · Cited by 133 · see citing works
FAD mutant PS-1 gene-targeted mice: increased Aβ42 and Aβ deposition without APP overproduction
Flood, D. (2002) · Neurobiology of Aging · doi:10.1016/s0197-4580(01)00330-x · Cited by 131 · see citing works
Steiner, H., Romig, H., Grim, M. G., Philipp, U., Pesold, B., Citron, M., Baumeister, R., & Haass, C. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.12.7615 · Cited by 126 · 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 · cited 1× · see citing works
“Mice expressing 5-fold excess of wild-type mouse APP also fail to produce amyloid deposits when mated to mice expressing human PS1dE9 despite raising the levels of MoAβ42 by more than 2 fold [21].”
BackgroundSelf-citationBRI2 (ITM2b) Inhibits A Deposition In Vivo
Kim, J., Miller, V. M., Levites, Y., West, K. J., Zwizinski, C. W., Moore, B. D., Troendle, F. J., Bann, M., Verbeeck, C., Price, R. W., et al. (2008) · Journal of Neuroscience · doi:10.1523/jneurosci.0891-08.2008 · Cited by 113 · cited 1× · see citing works
“The extraction and ELISA methods used have been described previously [25], with minor modification.”
MethodSelf-citationVariant Alzheimer’s disease with spastic paraparesis
Verkkoniemi, A., Somer, M., Rinne, J. O., Myllykangas, L., Crook, R., Hardy, J., Viitanen, M. H., Kalimo, H., & Haltia, M. (2000) · Neurology · doi:10.1212/wnl.54.5.1103 · Cited by 96 · see citing works
Variant Alzheimer Disease With Spastic paraparesis: Neuropathological phenotype
Verkkoniemi, A., Kalimo, H., Paetau, A. E., Somer, M., Iwatsubo, T., Hardy, J., & Haltia, M. (2001) · Journal of Neuropathology & Experimental Neurology · doi:10.1093/jnen/60.5.483 · Cited by 85 · see citing works
Savonenko, A. V., Xu, G. M., Price, D. L., Borchelt, D., & Markowska, A. L. (2003) · Neurobiology of Disease · doi:10.1016/s0969-9961(02)00012-8 · Cited by 82 · see citing works
Self-citationAyers, J. I., Xu, G. M., Pletniková, O., et al. (2014) · Acta Neuropathologica Communications · doi:10.1186/2051-5960-2-55 · Cited by 50 · see citing works
Self-citationReversible Pathologic and Cognitive Phenotypes in an Inducible Model of Alzheimer-Amyloidosis
Melnikova, T., Fromholt, S., Kim, H.-S., Lee, D., Xu, G. M., Price, A. R., Moore, B. D., Golde, T. E., Felsenstein, K. M., Savonenko, A. V., et al. (2013) · Journal of Neuroscience · doi:10.1523/jneurosci.4251-12.2013 · Cited by 48 · see citing works
Self-citationLesuisse, C. (2001) · Human Molecular Genetics · doi:10.1093/hmg/10.22.2525 · Cited by 45 · see citing works
Tebbenkamp, A. T. N., Green, C., Xu, G. M., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr176 · Cited by 42 · see citing works
Self-citationTebbenkamp, A. T. N., Swing, D., Tessarollo, L., & Borchelt, D. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr040 · Cited by 28 · see citing works
Self-citationAβ Deposition Does Not Cause the Aggregation of Endogenous Tau in Transgenic Mice
Xu, G. M., Gonzales, V., & Borchelt, D. (2002) · Alzheimer Disease & Associated Disorders · doi:10.1097/00002093-200207000-00011 · Cited by 19 · see citing works
Self-citationDynamics of Behavioral Disorders in Transgenic Mice with Modeled Alzheimer’s Disease
Ивановна, С. И., Байчурина, А. З., Makarova, E. A., Leushina, A. V., Kazakevich, Z. V., Gabdrakhmanova, M. R., Mukhamedyarov, M. A., & Zefirov, A. L. (2015) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-015-2821-0 · Cited by 3 · see citing works
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Alzheimer's disease: experimental models and reality
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Sasaguri, H., Nilsson, P., Hashimoto, S., Nagata, K., Saito, T., De Strooper, B., Hardy, J., Vassar, R., Winblad, B., & Saido, T. C. (2017) · The EMBO Journal · doi:10.15252/embj.201797397 · Cited by 793 · see citing works
Ilievski, V., Zuchowska, P. K., Green, S. J., Toth, P. T., Ragozzino, M. E., Le, K., Aljewari, H. W., O’Brien-Simpson, N. M., Reynolds, E. C., & Watanabe, K. (2018) · PLOS ONE · doi:10.1371/journal.pone.0204941 · Cited by 372 · see citing works
Wang, Z.-H., Xiang, J., Liu, X., Yu, S. P., Manfredsson, F. P., Sandoval, I. M., Wu, S., Wang, J.-Z., & Ye, K. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.06.054 · Cited by 238 · see citing works
- Authors
- Xu, G., Ran, Y., Fromholt, S. E., Fu, C., Yachnis, A. T., Golde, T. E., & Borchelt, D. R.
- Affiliations
- University of Florida Health (US)
- University of Florida (US)
- Corresponding author
- Borchelt, David R.
- Venue
- Acta Neuropathologica Communications
- Published
- 2015-11-14
- Volume
- 3
- Issue
- 1
- Pages
- 72-72
- ISSN
- 2051-5960 (ISSN-L)
- PMC
- PMC4644287
- OpenAlex
- W2172309362
- Cited by
- 65
- References
- 52
- Citations by year
- 2026: 5 · 2025: 8 · 2024: 3 · 2023: 5 · 2022: 5 · 2021: 11 · 2020: 6 · 2019: 9 · 2018: 7 · 2017: 3 · 2016: 3
- FWCI
- 3.19
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Acta Neuropathologica Communications (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- University of Florida Digital Collections (University of Florida) (submittedVersion, other-oa)
- Funders
- National Institute of Neurological Disorders and Stroke (NS047225)
- SanteFe HealthCare Alzheimer's Disease Research Center (ᅟᅟ)
- 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
- Alzheimer's disease, amyloid-beta, amyloid precursor protein, APP overexpression, familial Alzheimer's disease mutations, transgenic mouse model, extracellular amyloid deposition, neuritic plaques, white matter tracts, tetracycline-regulated expression
- MeSH terms
- Age Factors, Alzheimer Disease, Animals, Brain, Disease Models, Animal, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Humans, Mice, Inbred C57BL, Mice, Transgenic, Mutation, Neuroblastoma, Mass Spectrometry, Amyloid beta-Peptides, Cell Line, Tumor, Immunoprecipitation, Green Fluorescent Proteins, Mice, Presenilin-1, Plaque, Amyloid
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