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Author Notes:

Constatinos Paspalas:Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA,Tel.: +1-203-785-5230; Fax: + 1-203-785-5263.

Amy Arnsten:Department of Neuroscience, Yale School of Medicine, New Haven, CT, USA,+1-203-785-4431; Fax: +1-203-785-5263.

The authors are grateful to Dr. Peter R. Rapp of the National Institute on Aging, National Institutes of Health, for contributing brain tissue of a cognitively characterized rhesus macaque.

We thank Ms. Marianne Horn (Yale University) for her expert assistance with transcardial perfusions; Dr. Peter Davies (Litwin-Zucker Center for Alzheimer’s Disease and Memory Disorders) for the CP3 antibody; and Dr. Naruhiko Sahara (University of Florida) for his advice on tau biochemistry.

The authors have declared that no conflict of interest exists.


Research Funding:

Dr. Rapp’s contribution was supported in part by the Intramural Research Program of the NIA.

This work was supported by the National Institutes of Health (DP1AG047744, P50-AG047270, and RO1 AG043640); the Yerkes National Primate Research Center (OD P51OD11132); the Yale Alzheimer’s Disease Research Unit; and a gift in memory of Elsie Louise Torrance Higgs (Muinntir Bana-Ghaisgeach), who had faith that discoveries in brain research would help to alleviate human suffering.


  • Science & Technology
  • Life Sciences & Biomedicine
  • Clinical Neurology
  • Neurosciences & Neurology
  • Amyloid
  • Entorhinal cortex
  • Prefrontal cortex
  • Ryanodine receptor calcium leak
  • Tau phosphorylation
  • Animal model of disease
  • A-BETA
  • TAU

The aged rhesus macaque manifests Braak stage III/IV Alzheimer's-like pathology


Journal Title:

Alzheimer's and Dementia


Volume 14, Number 5


, Pages 680-691

Type of Work:

Article | Post-print: After Peer Review


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.

Copyright information:

© 2017 The Authors

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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