ArticlePloS one2013
Dissecting the gene dose-effects of the APOE ε4 and ε2 alleles on hippocampal volumes in aging and Alzheimer's disease.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers, 2 of them syntheses that pooled it.
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Who cites it
48 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- APOE ε4-associated hippocampal atrophy trajectories across the Alzheimer's disease continuum: a systematic review, meta-analysis, and longitudinal validation.Frontiers in aging neuroscience · 2026Pooled it
- Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis.Scientific reports · 2014Pooled it
- APOEmedRxiv : the preprint server for health sciences · 2025Article
- Genetic risk predictions using deep learning models with summary data.Frontiers in bioinformatics · 2025Article
- Blood biomarkers of neurodegeneration associate differently with amyloid deposition, medial temporal atrophy, and cerebrovascular changes in APOE ε4-enriched cognitively unimpaired elderly.Alzheimer's research & therapy · 2024Article
- Prominent genetic variants and epigenetic changes in post-traumatic stress disorder among combat veterans.Molecular biology reports · 2024Review
- Differences in Alzheimer's Disease-Related Pathology Profiles Across Apolipoprotein Groups.The journals of gerontology. Series A, Biological sciences and medical sciences · 2024Article
- Ethnic differences in the effects of apolipoprotein E ɛ4 and vascular risk factors on accelerated brain aging.Brain communications · 2024Article
- Impact of APOE-ε alleles on brain structure and cognitive function in healthy older adults: A VBM and DTI replication study.PloS one · 2024Article
- Effect of APOE ε4 genotype on amyloid-β, glucose metabolism, and gray matter volume in cognitively normal individuals and amnestic mild cognitive impairment.European journal of neurology · 2023Article
- APOE alleles are associated with sex-specific structural differences in brain regions affected in Alzheimer's disease and related dementia.PLoS biology · 2022Article
- Plasma high-density lipoprotein cargo is altered in Alzheimer's disease and is associated with regional brain volume.Journal of neurochemistry · 2022Article
- Heterogeneity in Alzheimer's Disease Diagnosis and Progression Rates: Implications for Therapeutic Trials.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2022Review
- Apolipoprotein E Genotype e2: Neuroprotection and Its Limits.Frontiers in aging neuroscience · 2022Review
- Genetic Variants Associated With Subjective Cognitive Decline in Patients With Migraine.Frontiers in aging neuroscience · 2022Article
- Studying APOE ɛ4 Allele Dose Effects with a Univariate Morphometry Biomarker.Journal of Alzheimer's disease : JAD · 2022Article
- Nonlinear interaction between APOE ε4 allele load and age in the hippocampal surface of cognitively intact individuals.Human brain mapping · 2021Article
- APOE2: protective mechanism and therapeutic implications for Alzheimer's disease.Molecular neurodegeneration · 2020Review
- Longitudinal association between hippocampus atrophy and episodic-memory decline in non-dementedAlzheimer's & dementia (Amsterdam, Netherlands) · 2020Article
- Associations between atherosclerosis and neurological diseases, beyond ischemia-induced cerebral damage.Reviews in endocrine & metabolic disorders · 2019Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
objectiveTo investigate whether there is a specific dose-dependent effect of the Apolipoprotein E (APOE) ε4 and ε2 alleles on hippocampal volume, across the cognitive spectrum, from normal aging to Alzheimer's Disease (AD). MATERIALS AND
methodsWe analyzed MR and genetic data on 662 patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database-198 cognitively normal controls (CN), 321 mild-cognitive impairment (MCI) subjects, and 143 AD subjects-looking for dose-dependent effects of the ε4 and ε2 alleles on hippocampal volumes. Volumes were measured using a fully-automated algorithm applied to high resolution T1-weighted MR images. Statistical analysis consisted of a multivariate regression with repeated-measures model.
resultsThere was a dose-dependent effect of the ε4 allele on hippocampal volume in AD (p = 0.04) and MCI (p = 0.02)-in both cases, each allele accounted for loss of >150 mm(3) (approximately 4%) of hippocampal volume below the mean volume for AD and MCI subjects with no such alleles (Cohen's d = -0.16 and -0.19 for AD and MCI, respectively). There was also a dose-dependent, main effect of the ε2 allele (p<0.0001), suggestive of a moderate protective effect on hippocampal volume-an approximately 20% per allele volume increase as compared to CN with no ε2 alleles (Cohen's d = 0.23).
conclusionThough no effect of ε4 was seen in CN subjects, our findings confirm and extend prior data on the opposing effects of the APOE ε4 and ε2 alleles on hippocampal morphology across the spectrum of cognitive aging.
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