Naturally occurring histological findings and Alzheimer's-like pathology in the brain of aging African green monkeys (Chlorocebus sabaeus)

Authors

Tatiana M. Corey, Center for Integrative Mammalian Research, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Oscar Illanes, Center for Integrative Mammalian Research, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.
Matthew Lawrence, Virscio, Inc., New Haven, Connecticut, USA.
Sylvia E. Perez, Department of Neurobiology, Barrow Neurological Institute, Phoenix, Arizona, USA.Follow
Shervin Liddie, Virscio, Inc., New Haven, Connecticut, USA.
John J. Callanan, Center for Integrative Mammalian Research, Ross University School of Veterinary Medicine, Basseterre, Saint Kitts and Nevis.

Document Type

Article

Abstract

Nonhuman primates (NHPs) are important to study the pathophysiology of neurodegenerative disease and evaluate therapies targeting the central nervous system (CNS). Understanding the age-associated incidence of natural CNS pathology in a given NHP species is critical to assess the safety of potential treatments for neurodegenerative disorders like Alzheimer's disease (AD). We describe background and age-related neuropathology in the St. Kitts African green monkey (AGM), a recognized translational model for neurodegenerative research, additionally defining the age progression of AD-associated neuropathology in this species. Seventy-one AGM brains were examined, representing age groups of 3-6 years (n = 20), 7-9 years (n = 20), 10-15 years (n = 20), and >15 years (n = 11). A subset of brains (n = 31) was assessed immunohistochemically for AD-related pathology, including expressions of Aβ, tau, and GFAP. Age-related microscopic findings included hemosiderosis, spheroid formation, neuronal lipofuscinosis and neuromelanosis, white matter and neuropil vacuolation, astrocytosis, and focal microgliosis. Non-age-related findings included perivascular ceroid-laden macrophages, meningeal melanosis, and vascular mineralization. Immunohistochemistry revealed 4G8-immunopositive Aβ plaques and vascular deposits in the prefrontal, frontal, cingulate, and temporal cortices of nine animals over 15 years of age, with associated increase in GFAP expression. In 12 animals, 11 over the age of 10 years, phosphorylated tau CP13-immunoreactive neurons, neuropil, and oligodendrocyte-like cells were seen in the prefrontal, frontal, cingulate, orbital, temporal, and entorhinal cortices as well as the hippocampus; no neurofibrillary tangles were observed. AD-related pathology showed an age-related development in cognitive-associated areas in the AGM, highlighting the value of the AGM as a natural model for these neurodegenerative diseases.

Keywords

African green monkey, Alzheimer's disease, aging, amyloid, animal model, neuropathology, nonhuman primate, tau

Publication Date

6-6-2023

Publication Title

The Journal of comparative neurology

E-ISSN

1096-9861

PubMed ID

37279778

Digital Object Identifier (DOI)

10.1002/cne.25494

Recommended Citation

Corey, Tatiana M.; Illanes, Oscar; Lawrence, Matthew; Perez, Sylvia E.; Liddie, Shervin; and Callanan, John J., "Naturally occurring histological findings and Alzheimer's-like pathology in the brain of aging African green monkeys (Chlorocebus sabaeus)" (2023). Translational Neuroscience. 2271.
https://scholar.barrowneuro.org/neurobiology/2271