Longitudinal white matter and cognitive development in pediatric carriers of the apolipoprotein ε4 allele
Open accessAbstract
We have previously demonstrated cross-sectional differences in magnetic resonance imaging (MRI) measurements of white matter myelin and gray matter in infants with or without the apolipoprotein ε4 allele, a major genetic risk factor for late-onset Alzheimer's disease (AD). In this study, we sought to compare longitudinal MRI white matter myelin and cognitive-behavioral changes in infants and young children with and without this allele. Serial MRI and cognitive tests were obtained on 223 infants and young children, including 74 ε4 carriers and 149 non-carriers, 2-68 months of age, matched for age, gestational duration, birth weight, sex ratio, maternal age, education, and socioeconomic status. Automated brain mapping algorithms and non-linear mixed models were used to characterize and compare trajectories of white matter myelin and cognitive-behavioral test scores. The APOE ε4 carriers had statistically significant differences in white matter myelin development, in the uncinate fasciculus, temporal lobe, internal capsule and occipital lobe. Additionally, ε4 carriers had a slightly greater rate of development in early learning composite a surrogate measure of IQ representative of expressive language, receptive language, fine motor, and visual skills, but displayed slightly lower non verbal development quotient scores a composite measure of fine motor and visual skills across the entire age range. This study supports the possibility that ε4 carriers have slightly altered rates of white matter and cognitive development in childhood. It continues to raise questions about the role of APOE in human brain development and the relevance of these developmental differences to the predisposition to AD.
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Infant APOE4-carriers exhibit alterations in myelin volume and cognitive maturation trajectories relative to APOE3/3-carriers.
“Infant APOE4-carriers exhibit alterations in myelin volume and cognitive maturation trajectories relative to APOE3/3-carriers34,35.”
From APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes (2022) · cites this paper as [35]
The Background and Discussion report differences in white-matter myelin and cognitive-development trajectories in infants and young children with the APOE ε4 allele. But the study compares ε4 carriers with all non-carriers, not specifically ε3/3 children, and uses myelin water fraction as a surrogate for myelin content rather than measuring myelin volume. No page numbers are available in our copy. (LLM, conf=0.86)
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- Dean DC Characterizing longitudinal white matter development during early childhood Brain Struct. Funct 220 4 2015 1921 1933 24710623 PMC4481335
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APOE4 impairs myelination via cholesterol dysregulation in oligodendrocytes
Blanchard, J. W., Akay, L. A., Davila-Velderrain, J., von Maydell, D., Mathys, H., Davidson, S. M., Effenberger, A., Chen, C.-Y., Maner-Smith, K., Hajjar, I., et al. (2022) · Nature · doi:10.1038/s41586-022-05439-w · Cited by 493 · see citing works
“Infant APOE4 carriers exhibit alterations in myelin volume and cognitive maturation trajectories relative to APOE3/3 carriers 34,35 .”
Vance, J. M., Farrer, L. A., Huang, Y., Cruchaga, C., Hyman, B. T., Pericak‐Vance, M. A., Goate, A. M., Greicius, M. D., Griswold, A. J., Haines, J. L., et al. (2024) · Annals of Neurology · doi:10.1002/ana.26864 · Cited by 52 · see citing works
- Authors
- Remer, J., Dean, D. C., Chen, K., Reiman, R. A., Huentelman, M. J., Reiman, E. M., & Deoni, S. C. L.
- Affiliations
- Brown University (US)
- University of Wisconsin–Madison (US)
- University of Arizona (US)
- Translational Genomics Research Institute (US)
- Gates Foundation (US)
- Corresponding author
- Remer, Justin
- Venue
- NeuroImage
- Publisher
- Elsevier BV
- Published
- 2020-11
- Volume
- 222
- Pages
- 117243
- ISSN
- 1053-8119 (ISSN-L)
- PMC
- PMC7779366
- OpenAlex
- W3058824227
- Cited by
- 33
- References
- 33
- Citations by year
- 2026: 6 · 2025: 9 · 2024: 5 · 2023: 7 · 2022: 5 · 2021: 1
- FWCI
- 2.37
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- NeuroImage (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (R00MH110596, SCD UG3OD023313)
- National Institute on Aging (P30 AG19610, R01 AG031581)
- Waisman Center (U54 HD090256)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Cognitive Abilities and Testing
- Keywords
- apolipoprotein E ε4 allele, apolipoprotein E, cognitive development, infants, young children, uncinate fasciculus, internal capsule, occipital lobe, temporal lobe, brain development, Alzheimer's disease risk, longitudinal brain MRI
- MeSH terms
- Aging, Alleles, Brain, Child, Child, Preschool, Cognition, Cross-Sectional Studies, Female, Heterozygote, Humans, Infant, Male, Myelin Sheath, Nerve Net, Apolipoprotein E4, White Matter
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