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The aged rhesus macaque manifests Braak stage III/IV Alzheimer's‐like pathology
Open accessAbstract
Introduction: An animal model of late‐onset Alzheimer's disease is needed to research what causes degeneration in the absence of dominant genetic insults and why the association cortex is particularly vulnerable to degeneration. Methods: We studied the progression of tau and amyloid cortical pathology in the aging rhesus macaque using immunoelectron microscopy and biochemical assays. Results: Aging macaques exhibited the same qualitative pattern and sequence of tau and amyloid cortical pathology as humans, reaching Braak stage III/IV. Pathology began in the young‐adult entorhinal cortex with protein kinase A‐phosphorylation of tau, progressing to fibrillation with paired helical filaments and mature tangles in oldest animals. Tau pathology in the dorsolateral prefrontal cortex paralleled but lagged behind the entorhinal cortex, not afflicting the primary visual cortex. Discussion: The aging rhesus macaque provides the long‐sought animal model for exploring the etiology of late‐onset Alzheimer's disease and for testing preventive strategies.
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“Recent studies have indicated that adult rhesus monkeys can effectively model AD-related neurodegeneration in primate brain, and may represent a more appropriate model for AD [636, 637].”
From Molecular and cellular mechanisms underlying the pathogenesis of Alzheimer’s disease (2020) · cites this paper as [637]
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Metadata
- Authors
- Paspalas, C. D., Carlyle, B. C., Leslie, S., Preuss, T. M., Crimins, J. L., Huttner, A. J., van Dyck, C. H., Rosene, D. L., Nairn, A. C., & Arnsten, A. F. T.
- Affiliations
- Yale University (US)
- Emory University (US)
- Department of Neuroscience Yale School of Medicine New Haven CT USA
- Boston University (US)
- Corresponding author
- Paspalas, Constantinos D.
- Arnsten, Amy F.T.
- ORCID
- Venue
- Alzheimer's & Dementia
- Publisher
- Wiley
- Published
- 2017-12-11
- Volume
- 14
- Issue
- 5
- Pages
- 680-691
- ISSN
- 1552-5260 (ISSN-L)
- 1552-5279
- PMC
- PMC6178089
- OpenAlex
- W2772269246
- Cited by
- 140
- References
- 51
- Citations by year
- 2026: 14 · 2025: 22 · 2024: 21 · 2023: 20 · 2022: 11 · 2021: 27 · 2020: 13 · 2019: 8 · 2018: 4
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Alzheimer s & Dementia (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion, cc-by-nc-nd)
- Funders
- National Institute on Aging
- National Institutes of Health (DP1AG047744, P50‐AG047270, RO1 AG043640)
- Yerkes National Primate Research Center, Emory University (OD P51OD11132)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Alzheimer's disease, rhesus monkeys
- MeSH terms
- Aging, Alzheimer Disease, Amyloid, Animals, Brain, Disease Models, Animal, Macaca mulatta, Phosphorylation, Microscopy, Immunoelectron, Neurofibrillary Tangles, tau Proteins, Prefrontal Cortex, Disease Progression, Entorhinal Cortex, Plaque, Amyloid
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