Introducing Human APOE into A β Transgenic Mouse Models

Tai, Leon M.; Youmans, Katherine L.; Jungbauer, Lisa; Yu, Chunjiang; LaDu, Mary Jo

doi:10.4061/2011/810981

Cited by 52Alzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration MechanismsDementia and Cognitive Impairment Research

Introducing Human APOE into A β Transgenic Mouse Models

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Tai, Leon M., Youmans, Katherine L., Jungbauer, Lisa, Yu, Chunjiang, LaDu, Mary Jo·2011·International Journal of Alzheimer’s Disease

DOI 10.4061/2011/810981PMC PMC3199079

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Abstract

Apolipoprotein E (apoE) and apoE/amyloid‐β (A β) transgenic (Tg) mouse models are critical to understanding apoE‐isoform effects on Alzheimer′s disease risk. Compared to wild type, apoE−/− mice exhibit neuronal deficits, similar to apoE4‐Tg compared to apoE3‐Tg mice, providing a model for A β‐independent apoE effects on neurodegeneration. To determine the effects of apoE on A β‐induced neuropathology, apoE−/− mice were crossed with A β‐Tg mice, resulting in a significant delay in plaque deposition. Surprisingly, crossing human‐apoE‐Tg mice with apoE−/−/A β‐Tg mice further delayed plaque deposition, which eventually developed in apoE4/A β‐Tg mice prior to apoE3/A β‐Tg. One approach to address h APOE‐induced temporal delay in A β pathology is an additional insult, like head injury. Another is crossing human‐apoE‐Tg mice with A β‐Tg mice that have rapid‐onset A β pathology. For example, because 5xFAD mice develop plaques by 2 months, the prediction is that human‐apoE/5xFAD‐Tg mice develop plaques around 6 months and 12 months before other human‐apoE/A β‐Tg mice. Thus, tractable models for human‐apoE/A β‐Tg mice continue to evolve.

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Female mice were excluded from this initial study for consistency, as apoE isoform-specific interaction with Aβ are known to be influenced by gender.
“Female mice were excluded from this initial study for consistency, as apoE isoform-specific interaction with A␤ are known to be influenced by gender (for review (44)).”
From APOE4-specific Changes in Aβ Accumulation in a New Transgenic Mouse Model of Alzheimer Disease (2012) · cites this paper as [44]
Sections 2.3 and 2.4 report that apoE isoform-related cognitive effects differ between female and male mice, supporting the general concern about sex differences. Sections 3.3 and 3.5 discuss isoform-specific Aβ pathology but do not establish that the apoE–Aβ interaction itself differs by sex. The paper also does not address the citing study’s decision to exclude female mice. (LLM, conf=0.82)
Experimental — accuracy not yet measured
In APP transgenic mouse models, genetic expression of human APOE4 promotes Aβ seeding, accelerates Aβ oligomerization and deposition in the brain.
“In APP transgenic mouse models, genetic expression of human APOE4 was found to promote Aβ seeding, accelerate Aβ oligomerization and deposition in the brain [455, 456].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [455]

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Research works printed but not linked: 6

[43]Bales KR Liu F Wu S Human APOE isoform-dependent effects on brain β-amyloid levels in PDAPP transgenic mice Journal of Neuroscience 2009 29 21 6771 6779 19474305 PMC6665579
[51]Youmans K Tai L Laxton K ApoE isoform-specific effects on Aβ pathology in EFAD mice In: Proceedings of the 2nd annual symposium of ApoE, ApoE Receptors, and Neurodegeneration 2011 Chicago, Ill, USA
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Authors: Tai, L. M., Youmans, K. L., Jungbauer, L., Yu, C., & LaDu, M. J.
Affiliations: University of Illinois Chicago (US)
Corresponding author: LaDu, Mary Jo
ORCID: Tai, Leon M.
Jungbauer, Lisa
Yu, Chunjiang
LaDu, Mary Jo
Venue: International Journal of Alzheimer’s Disease
Publisher: Wiley
Published: 2011-01
Volume: 2011
Issue: 1
Pages: 810981-810981
ISSN: 2090-0252 (ISSN-L)
2090-8024
DOI: 10.4061/2011/810981
PMC: PMC3199079
OpenAlex: W2064775133
Cited by: 52
References: 83
Citations by year: 2026: 2 · 2025: 1 · 2024: 2 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 5 · 2019: 6 · 2018: 4 · 2017: 6 · 2016: 3 · 2015: 2 · 2014: 5 · 2013: 2 · 2012: 4
FWCI: 2.40
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by
creativecommons.org/licenses/by/3.0/ (vor, 291 d)
Locations: International Journal of Alzheimer s Disease (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Figshare (submittedVersion, cc-by)
Funders: National Institute on Aging (P01AG03012801, ZEN-08-99900, UL1RR029879)
Alzheimer’s Association (P01AG03012801, ZEN-08-99900, UL1RR029879)
Center for Clinical and Translational Science (P01AG03012801, ZEN-08-99900, UL1RR029879)
Topics: Health Sciences › Medicine › Physiology › 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: apolipoprotein E, amyloid-beta, transgenic mouse model, Alzheimer's disease, APOE ε4, APOE3, amyloid plaques, plaque deposition, 5xFAD mice, traumatic brain injury, neurodegeneration

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Introducing Human APOE into A β Transgenic Mouse Models

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