Disrupted functional and structural networks in cognitively normal elderly subjects with the APOE ɛ4 allele
Open accessAbstract
As the Apolipoprotein E (APOE) ɛ4 allele is a major genetic risk factor for sporadic Alzheimer's disease (AD), which has been suggested as a disconnection syndrome manifested by the disruption of white matter (WM) integrity and functional connectivity (FC), elucidating the subtle brain structural and functional network changes in cognitively normal ɛ4 carriers is essential for identifying sensitive neuroimaging based biomarkers and understanding the preclinical AD-related abnormality development. We first constructed functional network on the basis of resting-state functional magnetic resonance imaging and a structural network on the basis of diffusion tensor image. Using global, local and nodal efficiencies of these two networks, we then examined (i) the differences of functional and WM structural network between cognitively normal ɛ4 carriers and non-carriers simultaneously, (ii) the sensitivity of these indices as biomarkers, and (iii) their relationship to behavior measurements, as well as to cholesterol level. For ɛ4 carriers, we found reduced global efficiency significantly in WM and marginally in FC, regional FC dysfunctions mainly in medial temporal areas, and more widespread for WM network. Importantly, the right parahippocampal gyrus (PHG.R) was the only region with simultaneous functional and structural damage, and the nodal efficiency of PHG.R in WM network mediates the APOE ɛ4 effect on memory function. Finally, the cholesterol level correlated with WM network differently than with the functional network in ɛ4 carriers. Our results demonstrated ɛ4-specific abnormal structural and functional patterns, which may potentially serve as biomarkers for early detection before the onset of the disease.
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Older individuals who are ApoE4 carriers have structural and functional alterations in AD-affected areas in the absence of cognitive dysfunction.
“older individuals who are ApoE4 carriers have structural and functional alterations in AD affected areas in the absence of cognitive dysfunction [15]”
From ApoE, ApoE Receptors, and the Synapse in Alzheimer's Disease (2017) · cites this paper as [15]
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Self-citation
- Authors
- Chen, Y., Chen, K., Zhang, J., Li, X., Shu, N., Wang, J., Zhang, Z., & Reiman, E. M.
- Affiliations
- Beijing Normal University (CN)
- Banner Alzheimer’s Institute (US)
- Corresponding author
- Zhang, Zhanjun
- Venue
- Neuropsychopharmacology
- Published
- 2014-11-18
- Volume
- 40
- Issue
- 5
- Pages
- 1181-1191
- ISSN
- 0893-133X (ISSN-L)
- 1740-634X
- PMC
- PMC4367462
- OpenAlex
- W2037875344
- Cited by
- 67
- References
- 62
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 9 · 2020: 11 · 2019: 5 · 2018: 7 · 2017: 8 · 2016: 5 · 2015: 5
- FWCI
- 3.07
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Neuropsychopharmacology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (81173460, 30873458, 81430100)
- China Academy of Chinese Medical Sciences (Z0175)
- Program for New Century Excellent Talents in University
- National Institute on Aging (R01AG031581, P30AG019610)
- Topics
- Life Sciences › Neuroscience › Cognitive Neuroscience › Functional Brain Connectivity Studies
- 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, Alzheimer's disease, preclinical Alzheimer's disease, white matter integrity, functional connectivity, brain network efficiency, parahippocampal gyrus, medial temporal lobe, memory function, cholesterol, neuroimaging biomarkers, cognitively normal elderly
- MeSH terms
- Aged, Alleles, Brain, Brain Mapping, Cholesterol, Female, Heterozygote, Humans, Magnetic Resonance Imaging, Male, Middle Aged, Neural Pathways, Neuropsychological Tests, Rest, ROC Curve, Apolipoprotein E4, Diffusion Tensor Imaging, White Matter
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