Evidence map›Paper›PMID 31367008›Full record

ReviewNature reviews. Neurology2019

Apolipoprotein E and Alzheimer disease: pathobiology and targeting strategies.

Yu Yamazaki, Na Zhao, Thomas R Caulfield, Chia-Chen Liu, Guojun Bu

Abstract readReview
In one paragraph

Review in Nature reviews. Neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 830 papers, 4 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
830citing papers in PubMed, 4 pooled it
70.1field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

830 citing papers in PubMed, 4 syntheses or guidelines pooled it, 1,388 citations in OpenAlex.

  1. Pooled it
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  9. Article
  10. Article
  11. Article
  12. Brain, behavior, & immunity - health · 2026
    Article
  13. Unveiling the pathogenesis and therapeutic strategies of Alzheimer's disease through cuproptosis.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2026
    Review
  14. Article
  15. Cross-disease protein aggregate interactions in neurodegeneration: from molecular mechanisms to therapeutic strategies.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  16. Article
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  19. Review
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770 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Yu YamazakiDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0002-0806-4960
Na ZhaoDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0001-8648-9422
Thomas R CaulfieldDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.ORCID http://orcid.org/0000-0002-1055-3069
Chia-Chen LiuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.
Guojun BuDepartment of Neuroscience, Mayo Clinic, Jacksonville, FL, USA. bu.guojun@mayo.edu.ORCID http://orcid.org/0000-0003-3491-1016
Mayo Clinic in Florida · USJacksonville College · US

Funding

Viral Vectors CoreP01NS074969 · NINDS · WASHINGTON UNIVERSITY · PI HOLTZMAN, DAVID M. · 2012 to 2021
$13.0M
Integrative translational discovery of vascular risk factors in aging and dementiaRF1AG051504 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN, ERTEKIN-TANER, NILUFER · 2015 to 2019
$9.8M
ApoE Receptor Pathways to Intraneuronal AbetaR01AG027924 · NIA · WASHINGTON UNIVERSITY · PI LI, YONGHE · 2006 to 2021
$3.7M
Impact of ApoE2 on aging-related conditionsRF1AG057181 · NIA · MAYO CLINIC JACKSONVILLE · PI KANEKIYO, TAKAHISA · 2018 to 2018
$3.7M
BRAIN LIPID METABOLISM, DENDRITES AND SYNAPSES IN AGING AND ALZHEIMER'S DISEASER01AG035355 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN · 2010 to 2019
$3.1M
ApoE isoform-specific therapy for Alzheimer diseaseRF1AG046205 · NIA · MAYO CLINIC JACKSONVILLE · PI ZHAO, NA · 2019 to 2019
$3.1M
ApoE pathway in cerebrovascular Aβ clearance in Alzheimer’s diseaseR37AG027924 · NIA · MAYO CLINIC JACKSONVILLE · PI BU, GUOJUN · 2017 to 2020
$2.4M
NIA NIH HHS R01 AG027924NIA NIH HHS R01 AG035355NIA NIH HHS R37 AG027924NIA NIH HHS RF1 AG046205NIA NIH HHS RF1 AG051504NIA NIH HHS RF1 AG057181NINDS NIH HHS P01 NS074969
6 · The paper itself

Abstract

Polymorphism in the apolipoprotein E (APOE) gene is a major genetic risk determinant of late-onset Alzheimer disease (AD), with the APOE*ε4 allele conferring an increased risk and the APOE*ε2 allele conferring a decreased risk relative to the common APOE*ε3 allele. Strong evidence from clinical and basic research suggests that a major pathway by which APOE4 increases the risk of AD is by driving earlier and more abundant amyloid pathology in the brains of APOE*ε4 carriers. The number of amyloid-β (Aβ)-dependent and Aβ-independent pathways that are known to be differentially modulated by APOE isoforms is increasing. For example, evidence is accumulating that APOE influences tau pathology, tau-mediated neurodegeneration and microglial responses to AD-related pathologies. In addition, APOE4 is either pathogenic or shows reduced efficiency in multiple brain homeostatic pathways, including lipid transport, synaptic integrity and plasticity, glucose metabolism and cerebrovascular function. Here, we review the recent progress in clinical and basic research into the role of APOE in AD pathogenesis. We also discuss how APOE can be targeted for AD therapy using a precision medicine approach.

Indexed as

Alzheimer DiseaseAmyloid beta-PeptidesApolipoproteins EBrainGenetic Predisposition to DiseaseHumansPlaque, AmyloidPolymorphism, GeneticAmyloid beta-PeptidesApoE protein, humanApolipoproteins E

Identifiers

PMID31367008
PMCPMC7055192
OpenAlexW2965401191

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.