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APOE interacts with tau PET to influence memory independently of amyloid PET in older adults without dementia
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Abstract
Introduction: Apolipoprotein E (APOE) interacts with Alzheimer's disease pathology to promote disease progression. We investigated the moderating effect of APOE on independent associations of amyloid and tau positron emission tomography (PET) with cognition. Methods: For 297 nondemented older adults from the Alzheimer's Disease Neuroimaging Initiative, regression equations modeled associations between cognition and (1) cortical amyloid beta (Aβ) PET levels adjusting for tau and (2) medial temporal lobe (MTL) tau PET levels adjusting for Aβ, including interactions with APOE ε4‐carrier status. Results: Adjusting for tau PET, Aβ was not associated with cognition and did not interact with APOE. In contrast, adjusting for Aβ PET, MTL tau was associated with all cognitive domains. Further, there was a stronger moderating effect of APOE on MTL tau and memory associations in ε4‐carriers, even among Aβ‐negative individuals. Discussion: Findings suggest that APOE may interact with tau independently of Aβ and that elevated MTL tau confers negative cognitive consequences in Aβ‐negative ε4 carriers.
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“Human tau positron emission tomography (PET) imaging studies found that tau PET burden is highly correlated with cognitive deficits and brain atrophy with APOE-ε4 increasing these associations (Therriault et al., 2020; Weigand et al., 2020).”
From Selective removal of astrocytic APOE4 strongly protects against tau-mediated neurodegeneration and decreases synaptic phagocytosis by microglia (2021) · cites this paper as Weigand et al., 2020
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Sorted by citations
Wang, C., Xiong, M., Gratuze, M., Bao, X., Shi, Y., Andhey, P. S., Manis, M., Schroeder, C., Yin, Z., Madore, C., et al. (2021) · Neuron · doi:10.1016/j.neuron.2021.03.024 · Cited by 334
ApoE4 reduction: An emerging and promising therapeutic strategy for Alzheimer's disease
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Metadata
- Authors
- Weigand, A. J., Thomas, K. R., Bangen, K. J., Eglit, G. M. L., Delano‐Wood, L., Gilbert, P. E., Brickman, A. M., Bondi, M. W., & Initiative, F. T. A. D. N.
- Affiliations
- San Diego State University/University of California San Diego Joint Doctoral Program San Diego
- Veterans Affairs San Diego Healthcare System San Diego California USA
- Department of Psychology San Diego State University California USA
- Taub Institute for Research on Alzheimer's Disease and the Aging Brain Department of Neurology College of Physicians and Surgeons Columbia University New York New York USA
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2020-09-04
- Volume
- 17
- Issue
- 1
- Pages
- 61-69
- ISSN
- 1552-5260
- 1552-5279
- Cited by
- 59
- References
- 13
- Language
- en
- Licence
- Funders
- National Science Foundation (DGE‐1650112, R01 AG049810, R01 AG054049)
- Alzheimer's Disease Neuroimaging Initiative (U01 AG024904)
- U.S. Department of Defense
- National Institute on Aging
- National Institute of Biomedical Imaging and Bioengineering
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