EFAD transgenic mice as a human APOE relevant preclinical model of Alzheimerʼns disease
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-modulated symptoms of AD pathology. From their first description in 2012, EFAD mice have enabled critical basic and therapeutic research. Here we review insights gleaned from the EFAD mice and summarize future directions.
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Even in homozygous APOE2/2 mice, prior reports have been inconsistent regarding further reductions in amyloid pathology compared with APOE3/3.
“Even in homozygous APOE2/2 mice, prior reports have been inconsistent regarding further reductions in amyloid pathology compared with APOE3/3 , re fl ecting ongoing debate 34,48,49 .”
From APOE2 attenuates APOE4-associated amyloid pathology and related toxicity in a mouse model of Alzheimer’s disease (2026) · cites this paper as [48]
In “APOE modulated AD symptoms exhibited in EFAD mice” (page unavailable), the paper reports equal E2FAD and E3FAD plaque measures and Aβ42 levels, supporting the point that APOE2/2 does not consistently show a further reduction in this model. It does not establish that prior mouse reports were inconsistent: its discussion of an “apparently contradictory literature” concerns human APOE2 genotypes and underpowered cohort studies. (LLM, conf=0.81)
Experimental — accuracy not yet measuredThe 5xFAD model used in this study provided a model with well-characterized APOE-dependent changes in amyloid pathology.
“Second, the 5xFAD model used in this study provided a model with well-characterized APOE-dependent changes in amyloid pathology55,63,64.”
From APOE4 to APOE2 allelic switching in mice improves Alzheimer’s disease-related metabolic signatures, neuropathology and cognition (2025) · cites this paper as [63]
The 'Development of the EFAD mouse model' section says 5xFAD mice were bred with human APOE targeted-replacement mice to create EFAD lines. The 'APOE modulated AD symptoms exhibited in EFAD mice' section documents APOE-dependent amyloid changes in those EFAD lines, but distinguishes them from ordinary 5xFAD mice, which express mouse apoE. Thus the source supports the changes in a 5xFAD-derived model, not in unmodified 5xFAD mice. (LLM, conf=0.87)
Experimental — accuracy not yet measuredBoth male and female E4FAD or APOE3+/+ mouse models with 5xFAD background (E3FAD) manifested with AD-related pathological, neuro-inflammatory, and behavioral phenotypes at 4-8 months of age, such as memory impairments measured by novel object recognition (NOR) tests with an inability to discriminate between novel and familiar objects.
“It was previously demonstrated that both male and female E4FAD or APOE3+/+ mouse models with 5xFAD background (E3FAD) manifested with AD-related pathological, neuro-inflammatory, and behavioral phenotypes at 4–8 months of age [29, 30], such as memory impairments measured by novel object recognition (NOR) tests with an inability to discriminate between novel and familiar objects [49].”
From Sex specific molecular networks and key drivers of Alzheimer’s disease (2023) · cites this paper as [30]
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References 360 · Cited by 93
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- Authors
- Tai, L. M., Balu, D., Avila-Munoz, E., Abdullah, L., Thomas, R., Collins, N., Valencia-Olvera, A. C., & LaDu, M. J.
- Affiliations
- University of Illinois Chicago (US)
- Roskamp Institute (US)
- Corresponding author
- LaDu, Mary Jo
- Venue
- Journal of Lipid Research
- Publisher
- Elsevier BV
- Published
- 2017-09
- Volume
- 58
- Issue
- 9
- Pages
- 1733-1755
- ISSN
- 0022-2275 (ISSN-L)
- PMC
- PMC5580905
- OpenAlex
- W2605159920
- Cited by
- 93
- References
- 360
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 26 · 2023: 7 · 2022: 11 · 2021: 10 · 2020: 12 · 2019: 11 · 2018: 2 · 2017: 3
- FWCI
- 0.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Lipid Research (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion)
- Funders
- National Institutes of Health (R21 AG051233, R21 AG044682, UH2NS100127)
- 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, apolipoprotein E, transgenic mouse model, preclinical models, amyloid-beta, tau pathology, lipid metabolism, therapeutic target
- MeSH terms
- Alzheimer Disease, Animals, Disease Models, Animal, Humans, Mice, Transgenic, Phenotype, Mice, Apolipoprotein E4
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