The DOI matches its Crossref record; 41 of the 42 references it cites were found in a registry or an index.
Time Course of the Development of Alzheimer-like Pathology in the Doubly Transgenic PS1+APP Mouse
Abstract
Doubly transgenic mice expressing both a mutated amyloid precursor protein and a mutated presenilin-1 protein accumulate A(beta) deposits as they age. The early A(beta) deposits were found to be primarily composed of fibrillar A(beta) and resembled compact amyloid plaques. As the mice aged, nonfibrillar A(beta) deposits increased in number and spread to regions not typically associated with amyloid plaques in Alzheimer's disease. The fibrillar, amyloid-containing deposits remained restricted to cortical and hippocampal structures and did not increase substantially beyond the 12-month time point. Even at early time points, the fibrillar deposits were associated with dystrophic neurites and activated astrocytes expressing elevated levels of glial fibrillary acidic protein. Microglia similarly demonstrated increased staining for complement receptor-3 in the vicinity of A(beta) deposits at early time points. However, when MHC-II staining was used to assess the degree of microglial activation, full activation was not detected until mice were 12 months or older. Overall, the regional pattern of A(beta) staining resembles that found in Alzheimer disease; however, a progression from diffuse A(beta) to more compact amyloid deposits is not observed in the mouse model. It is noted that the activation of microglia at 12 months is coincident with the apparent stabilization of fibrillar A(beta) deposits, raising the possibility that activated microglia might clear fibrillar A(beta) deposit…
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
“Animal models of amyloid pathology offer an experimental platform to studying AD (Gordon et al., 2002).”
From Early Alterations in Functional Connectivity and White Matter Structure in a Transgenic Mouse Model of Cerebral Amyloidosis (2014) · cites this paper as Gordon et al., 2002
In the citing paper
“In fact, based on the kinetics of appearance of reactivity markers, previous studies concluded that astrocyte alterations would precede microglia reactivity (Chun et al., 2018; Gordon et al., 2002; Tournier et al., 2020).”
From Inhibition of the mitochondrial pyruvate carrier in astrocytes reduces amyloid and tau accumulation in the 3xTgAD mouse model of Alzheimer's disease (2024) · cites this paper as Gordon et al., 2002
Citations
Cites
Measurement of protein using bicinchoninic acid
Smith, P. K., Krohn, R. I., Hermanson, G. T., Mallia, A. K., Gartner, F. H., Provenzano, M. D., Fujimoto, E. K., Goeke, N. M., Olson, B. J., & Klenk, D. C. (1985) · Analytical Biochemistry · doi:10.1016/0003-2697(85)90442-7 · Cited by 18,482
Inflammation and Alzheimer’s disease
Akiyama, H. (2000) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00124-x · Cited by 4,514
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
Immunization 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
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
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
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
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
Aβ peptide vaccination prevents memory loss in an animal model of Alzheimer's disease
Morgan, D., Diamond, D. M., Gottschall, P. E., Ugen, K. E., Dickey, C. A., Hardy, J., Duff, K., Jantzen, P. T., DiCarlo, G., Wilcock, D. M., et al. (2000) · Nature · doi:10.1038/35050116 · Cited by 1,506
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
Holcomb, L., Gordon, M. N., McGowan, E., Yu, X., Benkovic, S., Jantzen, P., Wright, K., Saad, I., Mueller, R., Morgan, D., et al. (1998) · Nature Medicine · doi:10.1038/nm0198-097 · Cited by 1,386
Self-citationBorchelt, 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
The Pathogenesis of Senile Plaques
DICKSON, D. W. (1997) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199704000-00001 · Cited by 753
Microglial response to amyloid plaques in APPsw transgenic mice.
Frautschy, S. A., Yang, F., Irrizarry, M., Hyman, B. T., Saido, T. C., Hsiao, K., & Cole, G. M. (1998) · Europe PMC (PubMed Central) · Cited by 592
(1997) · doi:10.1073/pnas.94.4.1550 · Cited by 535
Self-citationHolcomb, L. A., Gordon, M. N., Jantzen, P., Hsiao, K., Duff, K., & Morgan, D. (1999) · Behavior Genetics · doi:10.1023/a:1021691918517 · Cited by 353
Self-citationArendash, G. W., King, D. L., Gordon, M. N., Morgan, D., Hatcher, J. M., Hope, C. E., & Diamond, D. M. (2001) · Brain Research · doi:10.1016/s0006-8993(00)03186-3 · Cited by 349
Self-citationAssociation of Microglia with Amyloid Plaques in Brains of APP23 Transgenic Mice
Stalder, M., Phinney, A., Probst, A., Sommer, B., Staufenbiel, M., & Jucker, M. (1999) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)65423-5 · Cited by 345
Evidence for glial-mediated inflammation in aged APPSW transgenic mice
Benzing, W. C., Wujek, J. R., Ward, E. K., Shaffer, D. J., Ashe, K. H., Younkin, S. G., & Brunden, K. R. (1999) · Neurobiology of Aging · doi:10.1016/s0197-4580(99)00065-2 · Cited by 303
Lue, L. F., Brachova, L., CIVIN, W. H., & Rogers, J. (1996) · PubMed · Cited by 299
Hyman, B., Marzloff, K., & Arriagada, P. (1993) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199311000-00006 · Cited by 294
Lue, L.-F., Brachova, L., Civin, H. W., & Rogers, J. (1996) · Journal of Neuropathology and Experimental Neurology · doi:10.1097/00005072-199655100-00008 · Cited by 246 · cited 3×
“Indeed, cases referred to as high-plaque normals (autopsy brains with high amyloid loads but no indications of dementia ) generally do not stain for HLA-DR (26).”
BackgroundInfluentialSpectrum of morphological appearance of amyloid deposits in Alzheimer's disease
Wisniewski, H. M., Bancher, C., Barcikowska, M., Wen, G. Y., & Currie, J. (1989) · Acta Neuropathologica · doi:10.1007/bf00688170 · Cited by 220
Leverenz, J. B., & Raskind, M. A. (1998) · Experimental Neurology · doi:10.1006/exnr.1997.6777 · Cited by 214
Mehlhorn, G., Hollborn, M., & Schliebs, R. (2000) · International Journal of Developmental Neuroscience · doi:10.1016/s0736-5748(00)00012-5 · Cited by 199
Correlation between cognitive deficits and Aβ deposits in transgenic APP+PS1 mice
Gordon, M. N., King, D. L., Diamond, D. M., Jantzen, P. T., Boyett, K. W., Hope, C. E., Hatcher-Martin, J. M., DiCarlo, G., Gottschall, W. P. E., Morgan, D., et al. (2001) · Neurobiology of Aging · doi:10.1016/s0197-4580(00)00249-9 · Cited by 199
Self-citationStoltzner, S. E., Grenfell, T. J., Mori, C., Wisniewski, K. E., Wisniewski, T. M., Selkoe, D. J., & Lemere, C. A. (2000) · The American Journal of Pathology · doi:10.1016/s0002-9440(10)64753-0 · Cited by 187
McGowan, E. M., Sanders, S., Iwatsubo, T., Takeuchi, A., Saido, T. C., Zehr, C., Yu, X., Uljon, S., Wang, R., Mann, D. M. A., et al. (1999) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0243 · Cited by 183
Age-related changes in glial fibrillary acidic protein mRNA in the mouse brain
Goss, J. R., Finch, C. E., & Morgan, D. G. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90056-p · Cited by 170
Self-citationMann, D. M. A., Marcyniuk, B., Yates, P. O., Neary, D., & Snowden, J. S. (1988) · Neuropathology and Applied Neurobiology · doi:10.1111/j.1365-2990.1988.tb00880.x · Cited by 162
The concentration of glial fibrillary acidic protein increases with age in the mouse and rat brain
O'Callaghan, J. P., & Miller, D. B. (1991) · Neurobiology of Aging · doi:10.1016/0197-4580(91)90057-q · Cited by 152
Self-citationO'Callaghan, J. P. (1991) · Neurotoxicology and Teratology · doi:10.1016/0892-0362(91)90073-6 · Cited by 148
Self-citationMotte, J., & Williams, R. S. (1989) · Acta Neuropathologica · doi:10.1007/bf00687256 · Cited by 126
Exaggerated astrocyte reactivity after nigrostriatal deafferentation in the aged rat
Gordon, M. N., Schreier, W. A., Ou, X., Holcomb, L. A., & Morgan, D. (1997) · The Journal of Comparative Neurology · doi:10.1002/(sici)1096-9861(19971110)388:1 · Cited by 111
Self-citationTargeting Alzheimer amyloid plaques in vivo
Wengenack, T. M., Curran, G. L., & Poduslo, J. F. (2000) · Nature Biotechnology · doi:10.1038/78482 · Cited by 87
O'Callaghan, J. P., & Jensen, K. F. (1992) · PubMed · Cited by 80
Self-citationFunctional Phenotype in Transgenic Mice Expressing Mutant Human Presenilin-1
Barrow, P. A., Empson, R. M., Gladwell, S. J., Anderson, C. M., Killick, R., Yu, X., Jefferys, J. G. R., & Duff, K. (2000) · Neurobiology of Disease · doi:10.1006/nbdi.1999.0276 · Cited by 79
Pathological changes in frontal cortex from biopsy to autopsy in Alzheimer's disease
Bennett, D. A., Cochran, E. J., Saper, C. B., Leverenz, J. B., Gilley, D. W., & Wilson, R. S. (1993) · Neurobiology of Aging · doi:10.1016/0197-4580(93)90043-b · Cited by 67
Amyloid Precursor Protein (APP) in the Striatum in Alzheimerʼs Disease: An Immunohistochemical Study
Gearing, M., Wilson, R. W., Unger, E. R., Shelton, E. R., Chan, H. W., Masters, C. L., Beyreuther, K. T., & Mirra, S. S. (1993) · Journal of Neuropathology & Experimental Neurology · doi:10.1097/00005072-199301000-00004 · Cited by 40
The Pathogenesis and Progression of the Pathological Changes of Alzheimer's Disease
Mann, D. M. A. (1989) · Annals of Medicine · doi:10.3109/07853898909149200 · Cited by 37
Research works printed but not linked: 4
- Holcomb, 1998, Accelerated Alzheimer-type phenotype in transgenic mice carrying both mutant amyloid precursor protein and presenilin 1 transgenes, Nat. Med., 4, 97, 10.1038/nm0198-097 · DOI · Paper page
- Jantzen, 2000, Modification of microglial reactivity in mAPP/mPS1 transgenic mice using NCX-2216, Neurosci. Abstr., 30, 379.8
- Morgan, D., and M. N. Gordon. 1996. Aging and molecular biology. Pages 468–487 in D. Magnusson, Ed., The Lifespan Development of Individuals. Cambridge Univ. Press, New York.
- Savage, 1995, Elevated Aβ levels in Alzheimer's disease brain are associated with a selective accumulation of Aβ42 in parenchymal amyloid deposits, and both Aβ40 and Aβ42 in cerebrovascular deposits, Amyloid Int. J. Exp. Clin. Invest., 2, 234
Cited by
Sorted by citations
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
Self-citationKitazawa, M., Oddo, S., Yamasaki, T. R., Green, K. N., & LaFerla, F. M. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.2868-05.2005 · Cited by 697
Auld, D. S., Kornecook, T. J., Bastianetto, S., & Quirion, R. (2002) · Progress in Neurobiology · doi:10.1016/s0301-0082(02)00079-5 · Cited by 678
Wilcock, D. M., Rojiani, A. M., Rosenthal, A., Subbarao, S., Freeman, M. J., Gordon, M. N., & Morgan, D. (2004) · Journal of Neuroinflammation · doi:10.1186/1742-2094-1-24 · Cited by 392
Self-citationYoudim, K. A., Shukitt‐Hale, B., & Joseph, J. A. (2004) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2004.08.002 · Cited by 378
Metadata
- Authors
- Gordon, M. N., Holcomb, L. A., Jantzen, P. T., DiCarlo, G., Wilcock, D., Boyett, K. W., Connor, K., Melachrino, J., O'Callaghan, J. P., & Morgan, D.
- Affiliations
- University of South Florida (US)
- National Institute for Occupational Safety and Health (US)
- Venue
- Experimental Neurology
- Publisher
- Elsevier BV
- Published
- 2002-02
- Volume
- 173
- Issue
- 2
- Pages
- 183-195
- ISSN
- 0014-4886 (ISSN-L)
- OpenAlex
- W2152286012
- Cited by
- 247
- References
- 42
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 4 · 2023: 7 · 2022: 4 · 2021: 6 · 2020: 12 · 2019: 6 · 2018: 9 · 2017: 6 · 2016: 5 · 2015: 5 · 2014: 8 · 2013: 16 · 2012: 15
- FWCI
- 11.81
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Neurology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (R01AG018478, AG 15490, R01AG015490, AG18478)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- Alzheimer's disease, amyloid-beta, amyloid plaques, presenilin 1, amyloid precursor protein, microglial activation, complement receptor 3, MHC class II, astrocytes, glial fibrillary acidic protein, dystrophic neurites, mouse model
- MeSH terms
- Aging, Alzheimer Disease, Animals, Histocompatibility Antigens Class II, Astrocytes, Brain, Brain Stem, Cell Count, Disease Models, Animal, Glial Fibrillary Acidic Protein, Immunohistochemistry, Membrane Proteins, Mice, Transgenic, Neurons, Receptors, Complement, Neurites, Amyloid beta-Protein Precursor, Neurofibrillary Tangles, Microglia, Disease Progression, 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
