White Matter Alterations in Cognitively Normal apoE ɛ2 Carriers: Insight into Alzheimer Resistance?
Open accessAbstract
BACKGROUND AND PURPOSE: The basis for decreased vulnerability to AD among apoE ε2 carriers is unknown. The purpose of this study was to use diffusion tensor imaging to detect possible differences in white matter integrity between cognitively normal elderly apoE ε2 carriers and apoE ε3/ε3 controls. MATERIALS AND METHODS: Thirty-nine cognitively normal elderly individuals (19 heterozygous carriers of the apoE ε2 allele, 20 apoE ε3/ε3 subjects as controls) underwent diffusion tensor MR imaging on a 4T scanner. Fractional anisotropy, MD, and axial and radial diffusivity were compared using a ROI approach. In addition, an exploratory whole-brain analysis of fractional anisotropy between the 2 groups was undertaken using TBSS. RESULTS: apoE ε2 carriers had higher FA in the posterior cingulate white matter (P = .01) and anterior corpus callosum (P = .005) than apoE ε3/ε3 controls, secondary to lower radial diffusivity. No significant differences in the FA of the posterior corpus callosum, anterior cingulate white matter, or parahippocampal white matter were seen. Whole-brain TBSS analysis detected regions of higher FA in the apoE ε2 group in the superior longitudinal fasciculus, right thalamus, and the bilateral anterior limbs of the internal capsule, in addition to the posterior cingulum and corpus callosum (P < .005). There were no regions in which the apoE ε3/ε3 group had higher FA. CONCLUSIONS: apoE ε2 carriers harbor more robust white matter integrity that may be associated with decreased vulnerability to developing AD. This provides further evidence that regional DTI metrics may serve as early imaging biomarkers of AD risk.
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The few diffusion MRI studies evaluating APOE2 have generated mixed findings, with one study observing higher WM fractional anisotropy among APOE2 carriers, yet others reporting null effects.
“The few diffusion MRI studies evaluating APOE2 have similarly generated mixed findings, with one study observing higher WM fractional anisotropy among APOE2 carriers [14], yet others reporting null effects [7, 15].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [14]
One DTI study identified higher fractional anisotropy for APOE2 carriers than APOE3 homozygotes within a small cluster of the posterior cingulum.
“However, others reported no difference in WM integrity for APOE2 carriers [7, 15] and one DTI study identified higher fractional anisotropy for APOE2 carriers than APOE3 homozygotes within a small cluster of the posterior cingulum [14].”
From Effects of APOE2 and APOE4 on brain microstructure in older adults: modification by age, sex, and cognitive status (2024) · cites this paper as [14]
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“However, others reported no difference in WM integrity for APOE2 carriers [7, 15] and one DTI study identified higher fractional anisotropy for APOE2 carriers than APOE3 homozygotes within a small cluster of the posterior cingulum [14].”
BackgroundResult
- Authors
- Chiang, G. C., Zhan, W., Schuff, N., & Weiner, M. W.
- Affiliations
- San Francisco VA Medical Center (US)
- Venue
- American Journal of Neuroradiology
- Published
- 2012-03-01
- Volume
- 33
- Issue
- 7
- Pages
- 1392-1397
- ISSN
- 0195-6108 (ISSN-L)
- 1936-959X
- PMC
- PMC3951461
- OpenAlex
- W2100440179
- Cited by
- 25
- References
- 48
- Citations by year
- 2024: 4 · 2023: 1 · 2022: 2 · 2020: 3 · 2019: 1 · 2017: 1 · 2016: 6 · 2015: 2 · 2014: 2 · 2013: 3
- FWCI
- 1.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- American Journal of Neuroradiology (publishedVersion, cc-by)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- Funders
- U.S. Department of Defense (U01 AG024904)
- Michael J. Fox Foundation for Parkinson's Research
- Eli Lilly and Company
- Pfizer
- Biogen
- Synarc
- TauRx Pharmaceuticals
- Bayer HealthCare
- Irish Research Council
- Eisai
- Servier
- Ipsen
- National Institutes of Health (5u01ag024904-10, U01-AG024904)
- Genentech
- Allergan
- National Institute on Aging (U01-AG-024904, R01AG010897, P01AG012435, P01AG019724, P50AG023501)
- National Institute of Neurological Disorders and Stroke (R01NS031966)
- National Institute of Biomedical Imaging and Bioengineering (T32EB001631)
- National Center for Research Resources (U24RR021992, P41RR023953)
- Daiichi Sankyo Europe
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Keywords
- APOE ε2, white matter integrity, fractional anisotropy, radial diffusivity, cognitively normal elderly, corpus callosum, superior longitudinal fasciculus, thalamus, internal capsule, diffusion tensor imaging
- MeSH terms
- Aged, Alzheimer Disease, Brain, Cognition Disorders, Female, Heterozygote, Humans, Male, Nerve Fibers, Myelinated, Sensitivity and Specificity, Reproducibility of Results, Apolipoprotein E2, Diffusion Tensor Imaging, Disease Resistance
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