Apolipoprotein E affects the amount, form, and anatomical distribution of amyloid β-peptide deposition in homozygous APP V717F transgenic mice
Abstract
Apolipoprotein E (apoE) has been implicated as a risk factor for Alzheimer's disease and in the deposition, fibrillogenesis, and clearance of the amyloid beta-peptide (Abeta). To examine the in vivo interactions between apoE and Abeta deposition, we examined 12-month-old transgenic (tg) mice expressing human amyloid precursor protein (APP) with the V717F mutation (APP(V717F) homozygous) on an APOE null background. Elimination of APOE resulted in a redistribution and alteration in the character of Abeta deposition in homozygous APP(V717F) tg mice, with a dramatic reduction in cortical and dentate gyrus deposition, prominent increase in diffuse CA1 and CA3 deposition, and prevention of the formation of thioflavin-S-positive deposits. These alterations in Abeta deposition were not mediated by significant changes in regional APP expression, low-density lipoprotein receptor-related protein expression, or soluble Abeta levels. Thus, apoE in APP(V717F) tg mice not only affects the amount and form of Abeta deposition, but also the anatomical distribution of diffuse Abeta deposits. The APP(V717F) tg mouse can serve as a model to investigate genetic influences on the vulnerability of specific neuroanatomical regions to Abeta deposition.
Integrity signals
Registry
Cites
Statistics
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?
APOE exerts toxic effects on the cerebrovascular system and neurons and influences Aβ clearance, amyloid deposition, and tau-related neurodegeneration in an allele-dependent manner APOE4 > APOE3 > APOE2.
“APOE exerts toxic effects on the cerebrovascular system (694) and neurons (383, 384) and influences A 𝛃 clearance (60, 64, 98, 135, 256, 266, 278, 294, 315, 693), amyloid deposition (39, 256, 258, 266, 278, 314, 518, 612), and tau-related neurodegeneration (533) in an allele-dependent manner APOE4 > APOE3 > APOE2 .”
From Blood-Brain Barrier: From Physiology to Disease and Back (2019) · cites this paper as [278]
In several different Aβ plaque-depositing mice that are genetically engineered to express the human APOE isoforms instead of mouse APOE, APOE4 induces greater Aβ fibrillization and deposition in compact plaques relative to APOE3, whereas APOE2 markedly delays the onset and decreases the extent of Aβ plaque deposition.
“In several different Aβ plaque-depositing mice that are genetically engineered to express the human APOE isoforms instead of mouse APOE (Box 3), APOE4 induces greater Aβ fibrillization and deposition in compact plaques relative to APOE3, whereas APOE2 markedly delays the onset and decreases the extent of Aβ plaque deposition117–120.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [119]
Apoe knockout plaque-depositing mice still exhibit deposition of Aβ plaques, but the plaques are less compact and do not cause the synaptic and cognitive deficits typical of plaque-depositing mice with Apoe intact.
“Apoe knockout plaque-depositing mice highlight the complexity of the APOE–Aβ interaction, as these mice still exhibit deposition of Aβ plaques, but the plaques are less compact and do not cause the synaptic and cognitive deficits typical of plaque-depositing mice with Apoe intact117,119,122.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [119]
The process of APOE binding to TREM2 and promoting plaque compaction likely explains why both Apoe knockout and Trem2 knockout plaque-depositing mice exhibit reduced microglial reactivity against Aβ plaques and their plaques are less compact.
“This process is likely to explain why both Apoe knockout and Trem2 knockout plaque-depositing mice exhibit reduced microglial reactivity against Aβ plaques and their plaques are less compact117,119,122,155.”
From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [119]
In the PDAPP mouse model, the anatomical pattern of Aβ deposition was markedly different in the absence of apoE.
“Furthermore, in the PDAPP mouse model, the anatomical pattern of Aβ deposition was markedly different (Fagan et al., 2002; Irizarry et al., 2000).”
From The role of apolipoprotein E in Alzheimer's disease (2009) · cites this paper as Irizarry et al., 2000
The citation lists haven’t been fetched yet
References 34 · Cited by 93
- Authors
- Irizarry, M. C., Cheung, B. S., Rebeck, G. W., Paul, S. M., Bales, K. R., & Hyman, B. T.
- Affiliations
- Massachusetts General Hospital (US)
- Eli Lilly (United States) (US)
- Venue
- Acta Neuropathologica
- Published
- 2000-11-28
- Volume
- 100
- Issue
- 5
- Pages
- 451-458
- ISSN
- 0001-6322 (ISSN-L)
- 1432-0533
- OpenAlex
- W2041192235
- Cited by
- 93
- References
- 34
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2022: 3 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 3 · 2017: 1 · 2016: 1 · 2014: 4 · 2013: 1 · 2012: 3
- FWCI
- 3.89
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Acta Neuropathologica (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ag000793-05)
- National Institute on Aging (K08 AG00793)
- 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
- apolipoprotein E, Alzheimer's disease, amyloid fibril formation, amyloid precursor protein, hippocampus, cortical amyloid, LDL receptor-related protein
- MeSH terms
- Animals, Apolipoproteins E, Homozygote, Humans, Mice, Transgenic, Mutation, Peptide Fragments, Receptors, LDL, Tissue Distribution, Amyloid beta-Peptides, Amyloid beta-Protein Precursor, 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
