Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study
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The ε4 allelic variant of the Apolipoprotein E gene (APOE ε4) is the best-established genetic risk factor for late-onset Alzheimer's disease (AD). White matter (WM) microstructural damages measured with Diffusion Tensor Imaging (DTI) represent an early sign of fiber tract disconnection in AD. We examined the impact of APOE ε4 on WM microstructure in elderly individuals from the multicenter European DTI Study on Dementia. Voxelwise statistical analysis of fractional anisotropy (FA), mean diffusivity, radial and axial diffusivity (MD, radD and axD respectively) was carried out using Tract-Based Spatial Statistics. Seventy-four healthy elderly individuals - 31 APOE ε4 carriers (APOE ε4+) and 43 APOE ε4 non-carriers (APOE ε4-) -were considered for data analysis. All the results were corrected for scanner acquisition protocols, age, gender and for multiple comparisons. APOE ε4+ and APOE ε4- subjects were comparable regarding sociodemographic features and global cognition. A significant reduction of FA and increased radD was found in the APOE ε4+ compared to the APOE ε4- in the cingulum, in the corpus callosum, in the inferior fronto-occipital and in the inferior longitudinal fasciculi, internal and external capsule. APOE ε4+, compared to APOE ε4- showed higher MD in the genu, right internal capsule, superior longitudinal fasciculus and corona radiate. Comparisons stratified by center supported the results obtained on the whole sample. These findings support previous evidence in monocentric studies indicating a modulatory role of APOE ɛ4 allele on WM microstructure in elderly individuals at risk for AD suggesting early vulnerability and/or reduced resilience of WM tracts involved in AD.
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Prior diffusion MRI studies have identified microstructural white matter abnormalities in cognitively normal older APOE4 carriers, including increased mean diffusivity and reduced fractional anisotropy or restricted diffusion.
“Diffusion MRI studies have identified microstructural white matter (WM) abnormalities in cognitively normal older APOE4 carriers, including increased mean diffusivity and reduced fractional anisotropy or restricted diffusion [3–5]”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [4]
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Fluoro-2-Deoxy-D-Glucose (FDG)-PET in APOEε4 Carriers in the Australian Population
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APOE ϵ 4, Aging, and Effects on White Matter Across the Adult Life Span
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Mapping of ApoE4 related white matter damage using diffusion MRI
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2 of the 117 references couldn’t be matched to a known paper.
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White matter diffusion alterations precede symptom onset in autosomal dominant Alzheimer’s disease
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“In asymptomatic subjects at genetic risk of Alzheimer’s disease (Bendlin et al., 2010; Gold et al., 2010; Cavedo et al., 2017) or with abnormal Alzheimer’s disease biomarker values (Li et al., 2014; Racine et al., 2017), results are mixed including DTI-assessed white matter alterations…”
BackgroundPerivascular space fluid contributes to diffusion tensor imaging changes in white matter
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- Authors
- Cavedo, E., Lista, S., Rojkova, K., Chiesa, P. A., Houot, M., Brueggen, K., Blautzik, J., Bokde, A. L. W., Dubois, B., Barkhof, F., Pouwels, P. J. W., Teipel, S., & Hampel, H.
- Affiliations
- Centre National de la Recherche Scientifique (FR)
- Assistance Publique – Hôpitaux de Paris (FR)
- German Center for Neurodegenerative Diseases (DE)
- Ludwig-Maximilians-Universität München (DE)
- Trinity College Dublin (IE)
- Pitié-Salpêtrière Hospital (FR)
- Amsterdam Neuroscience (NL)
- Corresponding author
- Cavedo, Enrica
- ORCID
- Venue
- Neuroscience
- Publisher
- Elsevier BV
- Published
- 2017-08
- Volume
- 357
- Pages
- 119-133
- ISSN
- 0306-4522 (ISSN-L)
- OpenAlex
- W2624499846
- Cited by
- 40
- References
- 117
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 5 · 2023: 4 · 2022: 4 · 2021: 6 · 2020: 5 · 2019: 6 · 2018: 4
- FWCI
- 3.15
- Type
- journal article
- Language
- en
- Open access
- green
- discovery.ucl.ac.uk
- Locations
- Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- UCL Discovery (University College London) (submittedVersion)
- DZNE Pub (submittedVersion)
- Pure Amsterdam UMC (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Agence Nationale de la Recherche (ANR-10-IAHU-0006)
- AXA Research Fund (ANR-10-IAIHU-06)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- APOE ε4, white matter microstructure, white matter structural network, Alzheimer's disease risk, fractional anisotropy, radial diffusivity, mean diffusivity, cingulum, corpus callosum, inferior longitudinal fasciculus, internal capsule, superior longitudinal fasciculus, corona radiata, healthy older adults
- MeSH terms
- Aged, Aging, Brain, Europe, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Neural Pathways, Neuropsychological Tests, Retrospective Studies, Linear Models, Internationality, Apolipoprotein E4, Diffusion Tensor Imaging, White Matter
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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