Effects of APOE on brain white matter microstructure in healthy adults
Abstract
OBJECTIVES: APOE is related to cholesterol transport and clearance and brain white matter (WM) properties involving myelin, of which cholesterol is a major component. Diffusion tensor imaging enables in vivo investigations of brain WM, and could increase our understanding of the pathways leading to Alzheimer disease. The main objective was to investigate the association between APOE and diffusion tensor imaging-derived indices of WM microstructure. METHODS: Healthy participants were assessed on a range of neuropsychological measures, genotyped, and underwent MRI. A total of 203 volunteers (aged 21.1-69.9 years, mean = 47.6, SD = 14.9) with APOE genotypes ε2/ε3 (n = 30), ε3/ε3 (n = 113), and ε3/ε4 (n = 60) were included. RESULTS: There were widespread increases in mean and radial diffusion in carriers of the ε3/ε4 alleles compared with ε3/ε3 with medium to strong effect sizes (Cohen's d = 0.77-0.79). No interactions between genotype and age were observed, indicating relatively stable differences from early adulthood. The results were independent of presence of dementia in close family. We also observed increased mean and radial diffusion and decreased fractional anisotropy in carriers of the ε2/ε3 alleles compared with ε3/ε3 carriers. No significant differences were found between ε2/ε3 and ε3/ε4. CONCLUSIONS: APOE affects microstructural properties of the brain WM from early adulthood, but the specific allelic effects do not directly reflect the associated risk of developing Alzheimer disease. The role of APOE in cholesterol transport, the high density of cholesterol in myelin, and the specific effects on radial diffusivity support a putative functional role of APOE in modulating myelin-related processes in the brain.
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Some prior diffusion MRI studies observed null or inconsistent effects of APOE4 on white matter microstructure in cognitively normal older adults.
“whereas others observed null [6, 7] or inconsistent [8] effects.”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [8]
Westlye and colleagues observed higher WM mean and radial diffusivity for APOE2 carriers than APOE3 homozygotes.
“Consistent with our finding, Westlye and colleagues [8] observed higher WM mean and radial diffusivity for APOE2 carriers than APOE3 homozygotes.”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [8]
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- Authors
- Westlye, L. T., Reinvang, I., Rootwelt, H., & Espeseth, T.
- Affiliations
- Oslo University Hospital (NO)
- Venue
- Neurology
- Published
- 2012-11-06
- Volume
- 79
- Issue
- 19
- Pages
- 1961-1969
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- OpenAlex
- W2126833905
- Cited by
- 84
- References
- 42
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 6 · 2022: 7 · 2021: 3 · 2020: 7 · 2019: 5 · 2018: 4 · 2017: 4 · 2016: 13 · 2015: 8 · 2014: 16 · 2013: 2
- FWCI
- 6.28
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neurology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Keywords
- apolipoprotein E, white matter microstructure, APOE ε4, APOE ε2 allele, radial diffusivity, mean diffusivity, fractional anisotropy, myelin, cholesterol transport, Alzheimer's disease risk, diffusion tensor imaging, healthy adults
- MeSH terms
- Adult, Age Factors, Aged, Apolipoproteins E, Brain, Brain Mapping, Female, Genotype, Humans, Male, Middle Aged, Nerve Fibers, Myelinated, Neuropsychological Tests, Anisotropy, Young Adult, Diffusion Tensor Imaging
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