Evidence mapPaperPMID 33148345Full record

SynthesisAlzheimer's research & therapy2020

APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer's disease: a systematic review.

Sheina Emrani, Hirra A Arain, Cassandra DeMarshall, Tal Nuriel

Open access · goldAbstract readSystematic Review
In one paragraph

Synthesis in Alzheimer's research & therapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
103citing papers in PubMed, 3 pooled it
11.6field-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

103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 192 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026
    Article
  7. How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Review
  8. Article
  9. Article
  10. Article
  11. An automated plasma-based proteotyping immunoassay for APOE ε4 zygosity classification in Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
    Article
  12. Article
  13. Genetic analysis ofGenes & diseases · 2026
    Article
  14. Article
  15. Genetic Modifiers of Parkinson's Disease: A Case-Control Study.Annals of clinical and translational neurology · 2025
    Observational
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

43 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

4 authors at 3 institutions in 1 country.

Sheina EmraniDepartment of Psychology, Rowan University, 201 Mullica Hill Road, Glassboro, NJ, 08028, USA.
Hirra A ArainDepartment of Pathology and Cell Biology, Columbia University, 630 West 168th Street, New York, NY, 10032, USA.
Cassandra DeMarshallDepartment of Geriatrics and Gerontology, Rowan University School of Osteopathic Medicine, One Medical Center Drive, Stratford, NJ, 08084, USA.
Tal NurielDepartment of Pathology and Cell Biology, Columbia University, 630 West 168th Street, New York, NY, 10032, USA. tn2283@cumc.columbia.edu.ORCID 0000-0002-5252-8048
Rowan University · USColumbia University · USColumbia University Irving Medical Center · US

Funding

Elucidating the Temporal, Spatial and Cellular Effects of Differential APOE Isoform ExpressionR01AG070202 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 to 2025
$2.2M
Investigating the cause of APOE4-associated microglial activation and its resulting neurotoxicity of tauopathy-afflicted neuronsK01AG061264 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI Tal Nuriel · 2022 to 2023
$196k
NIA NIH HHS AG061264NIA NIH HHS K01 AG061264NIA NIH HHS R01 AG070202
6 · The paper itself

Abstract

Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer's disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4-) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4- AD patients. On the other hand, APOE4- AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4- AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations.

Indexed as

Alzheimer DiseaseApolipoprotein E4Apolipoproteins EAtrophyCognitionHumansApolipoprotein E4Apolipoproteins EADAlzheimer’s diseaseAPOEAPOE4Apolipoprotein EHeterogeneity

Identifiers

PMID33148345
PMCPMC7643479
OpenAlexW3095891654

What Socratic holds

Textmetadata
LicenceCC BY
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 Socratic graph.