Cited by 40Advanced Neuroimaging Techniques and ApplicationsDementia and Cognitive Impairment ResearchAlzheimer's disease research and treatments

Disrupted white matter structural networks in healthy older adult APOE ε4 carriers – An international multicenter DTI study

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Cavedo, Enrica, Lista, Simone, Rojkova, Katrine, Chiesa, Patrizia A., Houot, Marion, Brueggen, Katharina, Blautzik, Janusch, Bokde, Arun L.W. +5 more·2017·Neuroscience

Abstract

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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Crossref · 10.1016/j.neuroscience.2017.05.048

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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]”

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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
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
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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