The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Correlative Memory Deficits, Aβ Elevation, and Amyloid Plaques in Transgenic Mice
Abstract
Transgenic mice overexpressing the 695-amino acid isoform of human Alzheimer beta-amyloid (Abeta) precursor protein containing a Lys670 --> Asn, Met671 --> Leu mutation had normal learning and memory in spatial reference and alternation tasks at 3 months of age but showed impairment by 9 to 10 months of age. A fivefold increase in Abeta(1-40) and a 14-fold increase in Abeta(1-42/43) accompanied the appearance of these behavioral deficits. Numerous Abeta plaques that stained with Congo red dye were present in cortical and limbic structures of mice with elevated amounts of Abeta. The correlative appearance of behavioral, biochemical, and pathological abnormalities reminiscent of Alzheimer's disease in these transgenic mice suggests new opportunities for exploring the pathophysiology and neurobiology of this disease.
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
“Similar to AD, APP transgenic mouse models have elevated inflammation markers and gliosis associated with amyloid deposits (Games et al., 1995; Hsiao et al., 1996; Sturchler-Pierrat et al., 1997).”
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 Hsiao et al., 1996
In the citing paper
“The well established Tg2576 mouse model of AD, which overexpresses APP with the Swedish mutation (Hsiao et al., 1996), was used as a control in these studies and makes slightly more APP than our highest expressing line, Tg6799.”
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 Hsiao et al., 1996
In the citing paper
“In contrast, Tg2576 mice did not begin to deposit amyloid until ∼ 9-12 months of age (data not shown) (Hsiao et al., 1996).”
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 Hsiao et al., 1996
In the citing paper
“The first successful mouse models reproducing Aβ pathologies overexpressed human APP with either a single Swedish [25, 26] or Indiana [27] mutation.”
From Amyloid-β plaque formation and reactive gliosis are required for induction of cognitive deficits in App knock-in mouse models of Alzheimer’s disease (2019) · cites this paper as [25]
In the citing paper
“In addition, Tg2576 mice develop agedependent behavioral deficits as assessed by Y maze, T maze, and Morris water maze testing (Hsiao et al., 1996;Chapman et al., 1999;Westerman et al., 2000).”
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 Hsiao et al., 1996
In the citing paper
“The Tg2576 mouse model of Alzheimer's disease (Hsiao et al., 1996) expresses the Swedish mutation of APP (APP K670N,M671L ) at high level under control of the hamster prion protein (PrP) promoter.”
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 Hsiao et al., 1996
In the citing paper
“It overexpresses a mutant form of APP (isoform 695) with the Swedish mutation (KM670/671NL), resulting in elevated levels of amyloid beta (Aβ) and ultimately amyloid plaques [31].”
In the citing paper
“The observed relationship between VEEV TC-83 infection and the progression of AD may contribute to the development of AD, leading to elevated levels of Aβ and the formation of amyloid plaques [31].”
In the citing paper
“The Tg2576 model is one of the most well characterized and widely used mouse models of AD.”
In the citing paper
“the levels of A b in the brain are normally in the low nanomolar range, and in transgenic mouse models of brain amyloidosis they vary from 40 nM to 250 nM/kg from 3 to 12 months of age (54).”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [54]
In the citing paper
“Thus, this efflux transporter may be completely saturated by higher levels of A b , as are found in the brains of older transgenic APP animals (54-55), which in turn may lead to vascular accumulation of A b and development of prominent deposits of cerebrovascular amyloid, as recently described (56-57).”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [54]
In the citing paper
“there is a significant, timedependent, and progressive accumulation of the peptide with age in transgenic APP animals (54, 55)”
From Clearance of Alzheimer’s amyloid-β1-40 peptide from brain by LDL receptor–related protein-1 at the blood-brain barrier (2000) · cites this paper as [54]
In the citing paper
“Aβ deposits were rare in 6-mo-old Tg2576+/− brain but increased in number and size in 12-mo-old samples (Fig. 4, A and B), which is in agreement with a previous study (Hsiao et al., 1996).”
From VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology (2011) · cites this paper as Hsiao et al., 1996
In the citing paper
“They are also observed in 8-mo or older Tg2576 mice that express APPswe (Hsiao et al., 1996; Chapman et al., 1999; Rockenstein et al., 2007).”
From VPS35 haploinsufficiency increases Alzheimer’s disease neuropathology (2011) · cites this paper as Hsiao et al., 1996
In the citing paper
“In contrast to other mutant APP transgenic mice (Hsiao et al., 1996; Price et al., 1998), cerebellar Aβ accumulation was the earliest and most consistent feature in both lines of BRI-Aβ42 mice.”
From Aβ42 Is Essential for Parenchymal and Vascular Amyloid Deposition in Mice (2005) · cites this paper as Hsiao et al., 1996
In the citing paper
“Aβ plaques have also been detected in the retina of transgenic mouse models of AD (APPswe / PS1ΔE9, Tg2576AD, 3xTg-AD, PSAPP, 5xFAD; Hsiao et al., 1996; Holcomb et al., 1998; Takeuchi et al., 2000; Lukiw et al., 2001; Oddo et al., 2003; Kumar-Singh et al., 2005; Oakley et al., 2006; Philipson et al., 2010; Koronyo-Hamaoui et al., 2011).”
From The role of microglia in retinal neurodegeneration: Alzheimer’s disease, parkinson, and glaucoma. (2017) · cites this paper as Hsiao et al., 1996
In the citing paper
“This is different from the progression in Tg2576, which manifests synaptic damage at an early stage of pathological development (4.5 months) [68,69] with a corresponding decrease in synaptic density markers [70] prior to Aβ plaque development (10 months) [71] and cognitive deficiencies (one year) [72,73].”
From Centella Asiatica Improves Memory and Promotes Antioxidative Signaling in 5XFAD Mice (2019) · cites this paper as [71]
In the citing paper
“Tg2576 transgenic mice overexpressing the human APP695 protein with the ‘Swedish' mutation (APPswe), which show behavioural and histopathological abnormalities that closely mimic early AD21.”
From Dopamine neuronal loss contributes to memory and reward dysfunction in a model of Alzheimer’s disease (2017) · cites this paper as [21]
Citations
Cites
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
Mirra, S. S., Heyman, A., McKeel, D., Sumi, S. M., Crain, B. J., Brownlee, L. M., Vogel, F. S., Hughes, J. P., Belle, G. V., Berg, L., et al. (1991) · Neurology · doi:10.1212/wnl.41.4.479 · Cited by 4,961
Goate, 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
Terry, R. D., Masliah, E., Salmon, D. P., Butters, N., DeTeresa, R., Hill, R., Hansen, L. A., & Katzman, R. (1991) · Annals of Neurology · doi:10.1002/ana.410300410 · Cited by 4,397
Neurofibrillary tangles but not senile plaques parallel duration and severity of Alzheimer's disease
Arriagada, P. V., Growdon, J. H., Hedley-Whyte, E. T., & Hyman, B. T. (1992) · Neurology · doi:10.1212/wnl.42.3.631 · Cited by 2,668
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-citationAlzheimer-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
Diagnosis of Alzheimer's Disease
Khachaturian, Z. S. (1985) · Archives of Neurology · doi:10.1001/archneur.1985.04060100083029 · Cited by 2,499
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
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-citationA mutation in the Amyloid Precursor Protein Associated with Hereditary Alzheimer's Disease
Murrell, J. R., Farlow, M. R., Ghetti, B. F., & Benson, M. D. (1991) · Science · doi:10.1126/science.1925564 · Cited by 1,142
ON THE BINDING OF CONGO RED BY AMYLOID
Puchtler, H., Sweat, F., & Levine, M. I. (1962) · Journal of Histochemistry & Cytochemistry · doi:10.1177/10.3.355 · Cited by 1,133
Hendriks, 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
Self-citationSaido, T. C., Iwatsubo, T., Mann, D. M. A., Shimada, H., Ihara, Y., & Kawashima, S. (1995) · Neuron · doi:10.1016/0896-6273(95)90301-1 · Cited by 587
Hsiao, 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-citationMoran, P. M., Higgins, L. S., Cordell, B., & Moser, P. C. (1995) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.92.12.5341 · Cited by 345
Chimeric prion protein expression in cultured cells and transgenic mice
Scott, M. R. D., Köhler, R., FOSTER, D. B., & Prusiner, S. B. (1992) · Protein Science · doi:10.1002/pro.5560010804 · Cited by 250
Spontaneous Alternation Behavior
Dember, W. N., & Richman, C. L. (1989) · Springer eBooks · doi:10.1007/978-1-4613-8879-1 · Cited by 123
Koo, E. H., Sisodia, S. S., Cork, L. C., Unterbeck, A., Bayney, R. M., & Price, D. L. (1990) · Neuron · doi:10.1016/0896-6273(90)90446-m · Cited by 119
Transgenic mouse brain histopathology resembles early Alzheimer's disease
Higgins, L. S., Holtzman, D. M., Rabin, J., Mobley, W. C., & Cordell, B. (1994) · Annals of Neurology · doi:10.1002/ana.410350514 · Cited by 112
Mak, K., Yang, F., Vinters, H. V., Frautschy, S. A., & Cole, G. M. (1994) · Brain Research · doi:10.1016/0006-8993(94)91725-6 · Cited by 80
Self-citationMonoclonal antibody to the C-terminus of β-amyloid
Yang, F., Mak, K., Vinters, H. V., Frautschy, S. A., & Cole, G. M. (1994) · Neuroreport · doi:10.1097/00001756-199410270-00032 · Cited by 45
Self-citation
Research works printed but not linked: 5
- Chartier-Harlin M.-C., et al., ibid. 3538441991 .
- Mullan M., et al.ibid. p. 345.
- Saido T. C., et al.. ibid. 269152531994 .
- Kim K. S., et al.. Neurosci. Res. Commun. 71131990.
- Kim K. S., et al.. ibid. 21211988.
Cited by
Sorted by citations
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
The amyloid hypothesis of Alzheimer's disease at 25 years
Selkoe, D. J., & Hardy, J. (2016) · EMBO Molecular Medicine · doi:10.15252/emmm.201606210 · Cited by 6,164
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
“In contrast, Tg2576 mice did not begin to deposit amyloid until 9 –12 months of age (data not shown) (Hsiao et al., 1996).”
BackgroundMethodDiffusible, nonfibrillar ligands derived from Aβ 1–42 are potent central nervous system neurotoxins
Lambert, M. P., Barlow, A. K., Chromy, B. A., Edwards, C., Freed, R., Liosatos, M., Morgan, T. E., Rozovsky, I., Trommer, B., Viola, K. L., et al. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.11.6448 · Cited by 3,506
Metadata
- Authors
- Hsiao, K., Chapman, P., Nilsen, S., Eckman, C., Harigaya, Y., Younkin, S., Yang, F., & Cole, G.
- Affiliations
- University of Minnesota (US)
- University of Wales (GB)
- Mayo Clinic in Florida (US)
- University of California, Los Angeles (US)
- Corresponding author
- Hsiao, Karen
- Venue
- Science
- Published
- 1996-10-04
- Volume
- 274
- Issue
- 5284
- Pages
- 99-103
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2001210466
- Cited by
- 4,210
- References
- 23
- Citations by year
- 2026: 39 · 2025: 69 · 2024: 106 · 2023: 78 · 2022: 98 · 2021: 111 · 2020: 122 · 2019: 114 · 2018: 112 · 2017: 125 · 2016: 130 · 2015: 132 · 2014: 156 · 2013: 200 · 2012: 186
- FWCI
- 67.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01ag009009-07)
- National Institute on Aging (AG06656, AG9009, R01AG006656)
- National Institute of Neurological Disorders and Stroke (NS33249, R01NS033249)
- 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
- Alzheimer's disease, memory impairment, amyloid-beta, amyloid plaques, APP transgenic mice, APP695, Aβ(1-40), amyloid-beta 42, spatial learning, Congo red staining
- MeSH terms
- Aging, Alzheimer Disease, Animals, Brain, Brain Chemistry, Learning Disabilities, Memory Disorders, Mice, Transgenic, Peptide Fragments, Psychomotor Performance, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, Maze Learning, 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
