A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis

Caitlin S. Latimer, Carol A. Shively, C. Dirk Keene, Matthew J. Jorgensen, Rachel N. Andrews, Thomas C. Register, Thomas J. Montine, Angela M. Wilson, Bryan J. Neth, Akiva Mintz, Joseph A Maldjian, Christopher T. Whitlow, Jay R. Kaplan, Suzanne Craft

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Introduction: Nonhuman primates may serve as excellent models of sporadic age-associated brain β-amyloid deposition and Alzheimer's disease pathologic changes. We examined whether a vervet nonhuman primate model recapitulated pathologic, physiologic, and behavioral features of early Alzheimer's disease. Methods: Nine middle-aged (mean = 11.2 years) and nine aged (mean = 21.7 years) female vervet/African green monkeys underwent cerebrospinal fluid collection, gait speed measurement, and neuroimaging before neuropathologic assessment. Results: β-amyloid plaques were identified in all aged vervets and paired helical filament tau immunoreactivity was observed in all animals. Cerebrospinal fluid β-amyloid42 and gait speed correlated negatively with age and plaque density. Greater plaque and paired helical filament tau burden predicted reduced volumes and CMRg in several brain regions. Discussion: We observed a coordinated set of relationships among neuropathologic, cerebrospinal fluid, imaging, and behavioral modalities consistent with early Alzheimer's disease. Our results support future use of the vervet model to explore disease mechanisms, biomarkers, and novel therapeutic strategies.

Original languageEnglish (US)
JournalAlzheimer's and Dementia
DOIs
StateAccepted/In press - Jan 1 2018

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Keywords

  • Alzheimer's disease
  • Amyloid
  • Cerebrospinal fluid (CSF)
  • Model
  • Nonhuman primate
  • Tau

ASJC Scopus subject areas

  • Epidemiology
  • Health Policy
  • Developmental Neuroscience
  • Clinical Neurology
  • Geriatrics and Gerontology
  • Cellular and Molecular Neuroscience
  • Psychiatry and Mental health

Cite this

Latimer, C. S., Shively, C. A., Keene, C. D., Jorgensen, M. J., Andrews, R. N., Register, T. C., Montine, T. J., Wilson, A. M., Neth, B. J., Mintz, A., Maldjian, J. A., Whitlow, C. T., Kaplan, J. R., & Craft, S. (Accepted/In press). A nonhuman primate model of early Alzheimer's disease pathologic change: Implications for disease pathogenesis. Alzheimer's and Dementia. https://doi.org/10.1016/j.jalz.2018.06.3057