Effects of APOE on brain white matter microstructure in healthy adults
Westlye LT, Reinvang I, Rootwelt H, Espeseth T.. Neurology, 2012-10-24
Topic: Brain proteins, microglia and lab models
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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APA 7th
Westlye, L. T., Reinvang, I., Rootwelt, H., & Espeseth, T. (2012). Effects of APOE on brain white matter microstructure in healthy adults. Neurology. https://doi.org/10.1212/wnl.0b013e3182735c9c
Vancouver
Westlye LT, Reinvang I, Rootwelt H, Espeseth T. Effects of APOE on brain white matter microstructure in healthy adults. Neurology. 2012. doi:10.1212/wnl.0b013e3182735c9c. PMID: 23100402.
BibTeX
@article{westlye2012-23100402,
author = {Westlye, L. T. and Reinvang, I. and Rootwelt, H. and Espeseth, T.},
title = {{Effects of APOE on brain white matter microstructure in healthy adults}},
journal = {Neurology},
year = {2012},
doi = {10.1212/wnl.0b013e3182735c9c},
pmid = {23100402},
url = {https://doi.org/10.1212/wnl.0b013e3182735c9c}
}
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Key findings
- 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).
- 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.
Why it matters
Healthy adults carrying the APOE ε3/ε4 genotype showed widespread differences in brain white matter microstructure compared with ε3/ε3 carriers, and these differences appeared stable from early adulthood. This suggests APOE may affect brain structure long before any dementia symptoms, but it does not show that these changes cause Alzheimer disease.
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Study details
- Participants30
- Evidence strengthLow
How this study scored 48/100
Published in a leading specialty journal. Scored zero for study design, effect reported and randomized / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 1 / 5 | 2012 — within 20 year(s) of the newest study here |
| Sample size | 1 / 4 | 30 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomized / blinded | 0 / 2 | No randomization or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 4 / 7 | Cited 84 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 5.2 citations a year over 16 year(s) since 2012 |
| Impact for its field and year | 3 / 6 | Cited 5.8× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 2 / 6 | Cited by 3 other studies in this library |
| Still being cited | 1 / 4 | Cited 9 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 3 / 4 | Last-listed author Thomas Espeseth: h-index 57 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Oslo: institution h-index 1,024 (OpenAlex) |
| Multicenter collaboration | 1 / 3 | OpenAlex lists 3 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 23100402) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 48 / 100 | — |
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