SynthesisAlzheimer's research & therapy2020
APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer's disease: a systematic review.
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.
What it found
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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.
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.
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Who cites it
103 citing papers in PubMed, 3 syntheses or guidelines pooled it, 192 citations in OpenAlex.
- The role of APOE ε4 in modulating the relationship between non-genetic risk factors and dementia: a system review and meta-analysis.Journal of neurology · 2025Pooled it
- Digital Clock Drawing as an Alzheimer's Disease Susceptibility Biomarker: Associations with Genetic Risk Score and APOE in Older Adults.The journal of prevention of Alzheimer's disease · 2024Pooled it
- Confirmed Synergy Between the ɛ4 Allele of Apolipoprotein E and the Variant K of Butyrylcholinesterase as a Risk Factor for Alzheimer's Disease: A Systematic Review and Meta-Analysis.Journal of Alzheimer's disease reports · 2023Pooled it
- Genotypic Effects of the TOMM40'523 Variant and APOE on Longitudinal Cognitive Change over 4 Years: The TOMMORROW Study.The journal of prevention of Alzheimer's disease · 2023Trial
- Depletion of microglial compensation in glial network: Disease-associated response dynamics in the revised amyloid hypothesis.Neuroprotection (Chichester, England) · 2026Review
- The physiological effects of APOE genotype in healthy young/middle-aged individuals.Biological reviews of the Cambridge Philosophical Society · 2026Article
- How does type 2 diabetes modify the risk of Alzheimer's disease?Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Integrating contextual determinants and polygenic risk to examine dementia and late-life cognition in the Multi-Ethnic Study of Atherosclerosis.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Mapping heterogeneous brain structural subtypes in alzheimer's disease and mild cognitive impairment using normative models.Translational psychiatry · 2026Article
- Comparison of Methods for Sensitivity Analysis of Heterogeneous Treatment Effects in Observational Studies and Application to Alzheimer's Disease and Cognitive Decline.Statistics in medicine · 2026Article
- 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 · 2026Article
- Clinical and neuropsychological profile of Alzheimer's disease in Tunisia and the impact ofFrontiers in genetics · 2026Article
- Genetic analysis ofGenes & diseases · 2026Article
- Proteomic profiling of Alzheimer's disease and Vascular dementia reveals unique underlying signatures.medRxiv : the preprint server for health sciences · 2025Article
- Genetic Modifiers of Parkinson's Disease: A Case-Control Study.Annals of clinical and translational neurology · 2025Observational
- Blood pressure dynamic instability and neurodegeneration in older adults.Journal of Alzheimer's disease : JAD · 2025Article
- Brain volumes discriminate clinical dementia rating scale categories.Scientific reports · 2025Article
- Alpha-synuclein deposition patterns in Alzheimer's disease: association with cortical amyloid beta and variable tau load.Acta neuropathologica · 2025Article
- The association of human apolipoprotein ε4 with dementia, cognition, imaging, and plasma biomarkers of neurodegeneration in a sample of older adults in the Democratic Republic of the Congo.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
43 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 3 institutions in 1 country.
Funding
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.
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Registered trials
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.