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.
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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]
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“(Promoter: Hamster PrP Promoter, Symbol: Tg (APPSWE) 2576Kha, MGI ID: 2385631) In the Tg2576 mouse (Hsiao et al., 1996), the first presentation of cognitive deficits is seen at 5 months of age in spatial working memory (Arendash et al., 2004).”
BackgroundMethodInfluentialCharacterization of amyloid deposition in the APPswe/PS1dE9 mouse model of Alzheimer disease
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“To the extent that dendrite morphology and dendritic spines reflect fundamental structures necessary for the integration of signals in neocortical neurons, these changes likely contribute to the breakdown in electrophysiological integrity and behavioral abnormalities documented previously in Tg2576 mice (Hsiao et al.,…”
BackgroundMethodInfluentialThe Alzheimer's disease Beta-secretase enzyme, BACE1
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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
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