Sub-regional hippocampal injury is associated with fornix degeneration in Alzheimer’s disease.
Open accessAbstract
We examined in vivo evidence of axonal degeneration in association with neuronal pathology in Alzheimer's disease (AD) through analysis of fornix microstructural integrity and measures of hippocampal subfield atrophy. Based on known anatomical topography, we hypothesized that the local thickness of subiculum and CA1 hippocampus fields would be associated with fornix integrity, reflecting an association between AD-related injury to hippocampal neurons and degeneration of associated axon fibers. To test this hypothesis, multi-modal imaging, combining measures of local hippocampal radii with diffusion tensor imaging (DTI), was applied to 44 individuals clinically diagnosed with AD, 44 individuals clinically diagnosed with mild cognitive impairment (MCI), and 96 cognitively normal individuals. Fornix microstructural degradation, as measured by reduced DTI-based fractional anisotropy (FA), was prominent in both MCI and AD, and was associated with reduced hippocampal volumes. Further, reduced fornix FA was associated with reduced anterior CA1 and antero-medial subiculum thickness. Finally, while both lesser fornix FA and lesser hippocampal volume were associated with lesser episodic memory, only the hippocampal measures were significant predictors of episodic memory in models including both hippocampal and fornix predictors. The region-specific association between fornix integrity and hippocampal neuronal death may provide in vivo evidence for degenerative white matter injury in AD: axonal pathology that is closely linked to neuronal injury.
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Fornix microstructural degradation, as measured by reduced FA, is prominent in both MCI and AD.
“Fornix microstructural degradation, as measured by reduced FA, was prominent in both MCI and AD”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Lee et al., 2012
Fornix microstructural degradation may provide evidence of degenerative white matter injury in AD.
“and may provide evidence of degenerative white matter injury in AD (Lee et al., 2012).”
From Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging (2022) · cites this paper as Lee et al., 2012
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Age-dependent microstructure alterations in 5xFAD mice by high-resolution diffusion tensor imaging
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“Fornix microstructural degradation, as measured by reduced FA, was prominent in both MCI and AD, and may provide evidence of degenerative white matter injury in AD (Lee et al., 2012).”
Background
- Authors
- Lee, D. Y., Fletcher, E., Carmichael, O. T., Singh, B., Mungas, D., Reed, B., Martinez, O., Buonocore, M. H., Persianinova, M., & DeCarli, C.
- Affiliations
- Seoul National University (KR)
- University of California, Davis (US)
- Corresponding author
- Carmichael, Owen Thomas
- ORCID
- Venue
- Frontiers in Aging Neuroscience
- Publisher
- Frontiers Media SA
- Published
- 2012
- Volume
- 4
- Pages
- 1-1
- ISSN
- 1663-4365 (ISSN-L)
- PMC
- PMC3323836
- OpenAlex
- W2100651338
- Cited by
- 137
- References
- 57
- Citations by year
- 2024: 2 · 2023: 2 · 2022: 4 · 2021: 6 · 2020: 10 · 2019: 9 · 2018: 16 · 2017: 20 · 2016: 17 · 2015: 19 · 2014: 14 · 2013: 17 · 2012: 1
- FWCI
- 11.61
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- Frontiers in Aging Neuroscience (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AG10129, AG031563)
- National Institute on Aging (P30AG010129, R01AG021028, K01AG030514, R01AG010220, R01AG031563)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced Neuroimaging Techniques and Applications
- Keywords
- Alzheimer's disease, hippocampal subfields, subiculum, CA1, axonal degeneration, white matter injury, fractional anisotropy, hippocampal atrophy, mild cognitive impairment, episodic memory, diffusion tensor imaging
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