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Cited by 42Alzheimer's disease research and treatmentsDementia and Cognitive Impairment ResearchCholinesterase and Neurodegenerative Diseases

Targeting Apolipoprotein E for Alzheimer’s Disease: An Industry Perspective

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Suidan, Georgette L., Ramaswamy, Gayathri·2019·International Journal of Molecular Sciences
DOI 10.3390/ijms20092161PMC PMC6539182
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Abstract

Apolipoprotein E (apoE), a key lipid transport protein in the brain, is predominantly produced by astrocytes. Astrocytes are the most numerous cell type in the brain and are the main support network for neurons. They play a critical role in the synthesis and delivery of cholesterol in the brain. Humans have three common apoE isoforms, apoE2, apoE3 and apoE4, that show a strong genotype effect on the risk and age of onset for sporadic and late onset forms of Alzheimer’s disease (AD). Carriers of an ε4 allele have an increased risk of developing AD, while those with an ε2 allele are protected. Investigations into the contribution of apoE to the development of AD has yielded conflicting results and there is still much speculation about the role of this protein in disease. Here, we review the opposing hypotheses currently described in the literature and the approaches that have been considered for targeting apoE as a novel therapeutic strategy for AD. Additionally, we provide our perspective on the rationale for targeting apoE and the challenges that arise with respect to “drug-ability” of this target.

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  • Astrocytes provide the vast majority of the cholesterol required by mature neurons, and the APOE they produce is crucial for efficient cholesterol transport.

    “Astrocytes provide the vast majority of the cholesterol required by mature neurons, and the APOE they produce is crucial for efficient cholesterol transport142.”

    From Multifaceted roles of APOE in Alzheimer disease (2024) · cites this paper as [142]

    The Abstract says astrocytes play a critical role in cholesterol synthesis and delivery, and the Introduction says they are the predominant producers of apoE, which transports lipids to neurons. Section 3.5 adds that apoE is important for delivering cholesterol to neurons. The paper does not establish that astrocytes provide the vast majority of the cholesterol required specifically by mature neurons. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

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Authors
Suidan, G. L., & Ramaswamy, G.
Affiliations
Biogen (United States) (US)
Corresponding author
Ramaswamy, Gayathri
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2019-05-01
Volume
20
Issue
9
Pages
2161
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms20092161
PMC
PMC6539182
OpenAlex
W2942986481
Cited by
42
References
96
Citations by year
2026: 2 · 2025: 4 · 2024: 5 · 2023: 5 · 2022: 6 · 2021: 11 · 2020: 8
FWCI
0.74
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
  • Health Sciences › Medicine › Pharmacology › Cholinesterase and Neurodegenerative Diseases
Keywords
apolipoprotein E, Alzheimer's disease, APOE isoforms, APOE ε4, APOE2, APOE3, astrocytes, cholesterol transport, drug targetability, treatment options
MeSH terms
Alzheimer Disease, Animals, Apolipoproteins E, Astrocytes, Brain, Humans, Neuroprotective Agents, Molecular Targeted Therapy

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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