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Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques

GeroScience volume 42, pages 1733–1749 (2020)Cite this article

Abstract

As human lifespan increases and the population ages, diseases of aging such as Alzheimer’s disease (AD) are a major cause for concern. Although calorie restriction (CR) as an intervention has been shown to increase healthspan in many species, few studies have examined the effects of CR on brain aging in primates. Using postmortem tissue from a cohort of extremely aged rhesus monkeys (22–44 years old, average age 31.8 years) from a longitudinal CR study, we measured immunohistochemically labeled amyloid beta plaques in Brodmann areas 32 and 46 of the prefrontal cortex, areas that play key roles in cognitive processing, are sensitive to aging and, in humans, are also susceptible to AD pathogenesis. We also evaluated these areas for cortical neuron loss, which has not been observed in younger cohorts of aged monkeys. We found a significant increase in plaque density with age, but this was unaffected by diet. Moreover, there was no change in neuron density with age or treatment. These data suggest that even in the oldest-old rhesus macaques, amyloid beta plaques do not lead to overt neuron loss. Hence, the rhesus macaque serves as a pragmatic animal model for normative human aging but is not a complete model of the neurodegeneration of AD. This model of aging may instead prove most useful for determining how even the oldest monkeys are protected from AD, and this information may therefore yield valuable information for clinical AD treatments.

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Data availability

Contact corresponding author for data.

Abbreviations

Aβ:

Amyloid beta

AD:

Alzheimer’s disease

APOE:

Apolipoprotein E

APP:

Amyloid precursor protein

BA 32:

Brodmann Area 32 of the cingulate cortex

BA 46:

Brodmann Area 46 of the prefrontal cortex

CDC:

Centers for Disease Control and Prevention

CR:

Calorie restriction

MCI:

Mild cognitive impairment

NeuN:

Neuronal nucleic protein

NHP:

Nonhuman primate

NIA:

National Institute on Aging

PFC:

Prefrontal cortex

ROI:

Region of interest

TBS:

7.6 pH Tris-buffered saline

US:

United States of America

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Acknowledgments

The authors would like to acknowledge the contributions of Dr. Sathya Srinivasan in the Imaging and Histology core at the Oregon National Primate Research Center for his expertise in stereological methodology.

Code availability

Not applicable.

Funding

This work was supported by the National Institutes of Health (NIH) grants AG043640, AG055378, AG062220, OD011092 and the Intramural Research Program, National Institute on Aging, NIH.

Author information

Affiliations

  1. Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, 97239, USA

    GA Stonebarger & HF Urbanski

  2. Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR, 97006, USA

    GA Stonebarger, HF Urbanski & SG Kohama

  3. Department of Pathology, Oregon Health & Science University, Portland, OR, 97239, USA

    RL Woltjer

  4. Translational Gerontology Branch, National Institute on Aging Intramural Research Program, NIH, Dickerson, MD, 20842, USA

    KL Vaughan & JA Mattison

  5. Charles River, Wilmington, MA, 01867, USA

    KL Vaughan

  6. Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, 70808, USA

    DK Ingram

  7. Department of Anatomy and Neurobiology, Boston University School of Medicine, Boston, MD, 02218, USA

    PL Schultz, SM Calderazzo, JA Siedeman & DL Rosene

Authors
  1. GA Stonebarger
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  2. HF Urbanski
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  3. RL Woltjer
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  4. KL Vaughan
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  5. DK Ingram
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  6. PL Schultz
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  7. SM Calderazzo
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  8. JA Siedeman
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  9. JA Mattison
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  10. DL Rosene
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  11. SG Kohama
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Corresponding author

Correspondence to SG Kohama.

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This study makes use of animal tissue from a study approved by the National Institute on Aging Intramural Research Program Animal Care and Use Committee.

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Stonebarger, G., Urbanski, H., Woltjer, R. et al. Amyloidosis increase is not attenuated by long-term calorie restriction or related to neuron density in the prefrontal cortex of extremely aged rhesus macaques. GeroScience 42, 1733–1749 (2020). https://doi.org/10.1007/s11357-020-00259-0

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  • DOI: https://doi.org/10.1007/s11357-020-00259-0

Keywords

  • Aging
  • Alzheimer’s disease
  • Amyloid plaques
  • Diet
  • Neurodegeneration
  • Neuron number