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APOE‐ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies
Abstract
Introduction: Although the apolipoprotein E ε4‐allele (APOE‐ε4) is a susceptibility factor for Alzheimer's disease (AD) and dementia with Lewy bodies (DLB), its relationship with imaging and cognitive measures across the AD/DLB spectrum remains unexplored. Methods: We studied 298 patients (AD = 250, DLB = 48; 38 autopsy‐confirmed; NCT01800214) using neuropsychological testing, volumetric magnetic resonance imaging, and APOE genotyping to investigate the association of APOE‐ε4 with hippocampal volume and learning/memory phenotypes, irrespective of diagnosis. Results: Across the AD/DLB spectrum: (1) hippocampal volumes were smaller with increasing APOE‐ε4 dosage (no genotype × diagnosis interaction observed), (2) learning performance as assessed by total recall scores was associated with hippocampal volumes only among APOE‐ε4 carriers, and (3) APOE‐ε4 carriers performed worse on long‐delay free word recall. Discussion: These findings provide evidence that APOE‐ε4 is linked to hippocampal atrophy and learning/memory phenotypes across the AD/DLB spectrum, which could be useful as biomarkers of disease progression in therapeutic trials of mixed disease.
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From Cholesterol and matrisome pathways dysregulated in astrocytes and microglia (2022) · cites this paper as Saeed et al., 2018
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Cholesterol and matrisome pathways dysregulated in astrocytes and microglia
TCW, J., Qian, L., Pipalia, N. H., Chao, M. J., Liang, S. A., Shi, Y., Jain, B. R., Bertelsen, S. E., Kapoor, M., Marcora, E., et al. (2022) · Cell · doi:10.1016/j.cell.2022.05.017 · Cited by 411
APOE ε4, white matter hyperintensities, and cognition in Alzheimer and Lewy body dementia
Mirza, S. S., Saeed, U., Knight, J., Ramirez, J., Stuss, D. T., Keith, J., Nestor, S. M., Yu, D., Swardfager, W., Rogaeva, E., et al. (2019) · Neurology · doi:10.1212/wnl.0000000000008377 · Cited by 67
Self-citationAl‐Amin, M. M., Kim, B., Karahan, H., Tate, M. D., Walsh, S. P., Puntambekar, S. S., Bissel, S. J., Lamb, B. T., Wang, N., & Kim, J. (2025) · Alzheimer's & Dementia · doi:10.1002/alz.70791 · Cited by 6
Metadata
- Authors
- Saeed, U., Mirza, S. S., MacIntosh, B. J., Herrmann, N., Keith, J., Ramirez, J., Nestor, S. M., Yu, Q., Knight, J., Swardfager, W., Potkin, S. G., Rogaeva, E., St. George‐Hyslop, P., Black, S. E., & Masellis, M.
- Affiliations
- Institute of Medical Science Faculty of Medicine University of Toronto Toronto ON Canada
- Division of Neurology Department of Medicine University of Toronto Toronto ON Canada
- Hurvitz Brain Sciences Research Program Sunnybrook Research Institute University of Toronto Toronto ON Canada
- Department of Anatomical Pathology Sunnybrook Health Sciences Centre University of Toronto Toronto ON Canada
- LC Campbell Cognitive Neurology Research Unit Sunnybrook Research Institute University of Toronto Toronto ON Canada
- Data Science Institute and Medical School Lancaster University Lancaster UK
- Department of Psychiatry and Human Behavior University of California Irvine CA USA
- Tanz Centre for Research in Neurodegenerative Diseases University of Toronto Toronto ON Canada
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2018-05-18
- Volume
- 14
- Issue
- 9
- Pages
- 1137-1147
- ISSN
- 1552-5260
- 1552-5279
- Cited by
- 48
- References
- 12
- Language
- en
- Funders
- Canadian Institutes of Health Research (MOP13129)
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- Saeed, U., Mirza, S. S., MacIntosh, B. J., Herrmann, N., Keith, J., Ramirez, J., Nestor, S. M., Yu, Q., Knight, J., Swardfager, W., Potkin, S. G., Rogaeva, E., St. George‐Hyslop, P., Black, S. E., & Masellis, M. (2018). APOE‐ε4 associates with hippocampal volume, learning, and memory across the spectrum of Alzheimer's disease and dementia with Lewy bodies. Alzheimer's & Dementia. https://doi.org/10.1016/j.jalz.2018.04.005
