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Cited by 149Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchNeuroinflammation and Neurodegeneration Mechanisms

APOE in the normal brain

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Flowers, Sarah A., Rebeck, G. William·2020·Neurobiology of Disease
DOI 10.1016/j.nbd.2019.104724PMC PMC7002287
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Abstract

The APOE4 protein affects the primary neuropathological markers of Alzheimer's disease (AD): amyloid plaques, neurofibrillary tangles, and gliosis. These interactions have been investigated to understand the strong effect of APOE genotype on risk of AD. However, APOE genotype has strong effects on processes in normal brains, in the absence of the hallmarks of AD. We propose that CNS APOE is involved in processes in the normal brains that in later years apply specifically to processes of AD pathogenesis. We review the differences of the APOE protein found in the CNS compared to the plasma, including post-translational modifications (glycosylation, lipidation, multimer formation), focusing on ways that the common APOE isoforms differ from each other. We also review structural and functional studies of young human brains and control APOE knock-in mouse brains. These approaches demonstrate the effects of APOE genotype on microscopic neuron structure, gross brain structure, and behavior, primarily related to the hippocampal areas. By focusing on the effects of APOE genotype on normal brain function, approaches can be pursued to identify biomarkers of APOE dysfunction, to promote normal functions of the APOE4 isoform, and to prevent the accumulation of the pathologic hallmarks of AD with aging.

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  • Proteinaceous lipid nanoparticles (LNPs) are the main vehicles for lipid transport between cells in mammals.

    “Proteinaceous lipid nanoparticles (LNPs) are the main vehicles for lipid transport between cells in mammals.1–4”

    From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [1]

    The “CNS APOE protein structure” and “APOE CNS lipoproteins” sections describe lipid-associated lipoprotein particles and their role in lipid transport. They do not establish that these particles are the main vehicles for lipid transport between cells throughout mammals; that broader, comparative claim is unsupported by this source. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • ApoE mediates the transport of cholesterol and other lipids, which is essential for synaptogenesis and neuronal growth/survival in normal brains.

    “apoE mediates the transport of cholesterol and other lipids, which is essential for synaptogenesis and neuronal growth/survival in normal brains”

    From ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease (2022) · cites this paper as Flowers & Rebeck 2020

    The CNS APOE lipoproteins section (page unavailable) describes APOE associating with brain lipids and identifies lipid transport as one of its functions. The CNS APOE structure-function relationships section says lipid delivery to neurons could increase resilience and APOE can promote neural complexity. It does not establish that this transport is essential for synaptogenesis or neuronal growth and survival, as the claim states. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Flowers, S. A., & Rebeck, G. W.
Affiliations
Georgetown University (US)
Corresponding author
Rebeck, G. William
ORCID
Venue
Neurobiology of Disease
Publisher
Elsevier BV
Published
2020-03
Volume
136
Pages
104724
ISSN
0969-9961 (ISSN-L)
DOI
10.1016/j.nbd.2019.104724
PMC
PMC7002287
OpenAlex
W2996808820
Cited by
149
References
34
Citations by year
2026: 18 · 2025: 24 · 2024: 20 · 2023: 21 · 2022: 26 · 2021: 25 · 2020: 14
FWCI
2.74
Type
journal article
Language
en
Open access
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  • Neurobiology of Disease (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Institutes of Health
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
APOE ε4, Alzheimer's disease, APOE genotype, normal brain function, post-translational modification, APOE isoforms, glycosylation, lipid modification, multimer formation, hippocampus, biomarkers, aging, amyloid plaques, neurofibrillary tangles, gliosis
MeSH terms
Aging, Alzheimer Disease, Animals, Brain, Humans, Neurons, Neurofibrillary Tangles, Apolipoprotein E4

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 ›

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