Hippocampal CA1 apical neuropil atrophy in mild Alzheimer disease visualized with 7-T MRI
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OBJECTIVES: In Alzheimer disease (AD), mounting evidence points to a greater role for synaptic loss than neuronal loss. Supporting this notion, multiple postmortem studies have demonstrated that the hippocampal CA1 apical neuropil is one of the earliest sites of pathology, exhibiting tau aggregates and then atrophy before there is substantial loss of the CA1 pyramidal neurons themselves. In this cross-sectional study, we tested whether tissue loss in the CA1 apical neuropil layer can be observed in vivo in patients with mild AD. METHODS: We performed ultra-high-field 7-T MRI on subjects with mild AD (n = 14) and age-matched normal controls (n = 16). With a 2-dimensional T2*-weighted gradient-recalled echo sequence that was easily tolerated by subjects, we obtained cross-sectional slices of the hippocampus at an in-plane resolution of 195 μm. RESULTS: On images revealing the anatomic landmarks of hippocampal subfields and strata, we observed thinning of the CA1 apical neuropil in subjects with mild AD compared to controls. By contrast, the 2 groups exhibited no difference in the thickness of the CA1 cell body layer or of the entire CA1 subfield. Hippocampal volume, measured on a conventional T1-weighted sequence obtained at 3T, also did not differentiate these patients with mild AD from controls. CONCLUSIONS: CA1 apical neuropil atrophy is apparent in patients with mild AD. With its superior spatial resolution, 7-T MRI permits in vivo analysis of a very focal, early site of AD pathology.
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Normal volume of the CA1 subfield was reported by Lim et al. and by Kerchner et al.
“Normal volume of the CA1 subfield was reported by Lim et al. [31], who used the same automated segmentation protocol used in the present study, and by Kerchner et al. [32], who inferred volume by measuring the thickness of the CA1 subfield”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [32]
The studies by Lim et al. and Kerchner et al. included patients whose disease severity was similar to that of the present study's patients.
“both of the aforementioned studies included patients whose disease severity was similar to that of our patients (as indicated by MMSE and CDR scores).”
From Atrophy of presubiculum and subiculum is the earliest hippocampal anatomical marker of Alzheimer's disease (2015) · cites this paper as [32]
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- Authors
- Kerchner, G. A., Hess, C. P., Hammond-Rosenbluth, K. E., Xu, D., Rabinovici, G. D., Kelley, D. A. C., Vigneron, D. B., Nelson, S. J., & Miller, B. L.
- Affiliations
- University of California, San Francisco (US)
- From the Stanford Center for Memory Disorders (G.A.K.), Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford; Memory and Aging Center, Department of Neurology (G.A.K., G.D.R., B.L.M.), and Departments of Radiology and of Bioengineering and Therapeutic Sciences (C.P.H., D.X., D.B.V., S.J.N.), University of California, San Francisco; UCSF/UCB Joint Graduate Group in Bioengineering (K.E.H.-R.), University of California, San Francisco, and University of...
- Venue
- Neurology
- Published
- 2010-10-12
- Volume
- 75
- Issue
- 15
- Pages
- 1381-1387
- ISSN
- 0028-3878 (ISSN-L)
- 1526-632X
- PMC
- PMC3013485
- OpenAlex
- W2036550078
- Cited by
- 193
- References
- 39
- Citations by year
- 2026: 9 · 2025: 6 · 2024: 9 · 2023: 12 · 2022: 4 · 2021: 10 · 2020: 18 · 2019: 10 · 2018: 10 · 2017: 15 · 2016: 11 · 2015: 19 · 2014: 22 · 2013: 10 · 2012: 11
- FWCI
- 8.28
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Neurology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Larry L. Hillblom Foundation
- National Institutes of Health
- National Institute on Aging (K23AG031861, P01AG019724)
- 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 MRI Techniques and Applications
- Keywords
- Alzheimer's disease, mild Alzheimer disease, hippocampal CA1, synaptic loss, ultra-high field MRI, 7T MRI, hippocampal subfields, hippocampal volume
- MeSH terms
- Aged, Alzheimer Disease, Atrophy, Female, Humans, Image Processing, Computer-Assisted, Magnetic Resonance Imaging, Male, Mental Status Schedule, Middle Aged, Case-Control Studies, Statistics, Nonparametric, Neuropil, CA1 Region, Hippocampal
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