Bearded capuchin monkey as a model for Alzheimer’s disease (AD) research
Roberta Diehl Rodriguez, Maria Clotilde Henriques Tavares, Sonia Brucki, Leonel Tadao Takada, Lea T. Grinberg, Maria Concepción Gracía Otaduy, Maria Da Graça Morais Martin, Claudia Costa Leite, Carlos Tomaz, Ricardo Nitrini- Psychiatry and Mental health
- Cellular and Molecular Neuroscience
- Geriatrics and Gerontology
- Neurology (clinical)
- Developmental Neuroscience
- Health Policy
- Epidemiology
Abstract
Background
The absence of a natural animal model is one of the main challenges to research in AD. AD‐type pathology has been described in chimpanzees and other primates’ brains. The bearded capuchin monkey (Sapajus libidinosus) is a New World primate that attracted attention mainly due to its skill in creating and using tools. We evaluated the brains of three captive capuchins (9, 29 and 33 years‐old) who died from natural causes at the Primate Center of University of Brasilia.
Method
Whole brain was fixed in 4% buffered paraformaldehyde within 12 hours of death for three weeks. Structural 7T MRI was acquired in one case before brain slicing. Consecutive coronal sections from the fixed brain were embedded in paraffin, and 5um sections from paraffin blocks were used for staining and immunohistochemistry evaluation. All brain sections were stained with hematoxylin and eosin. Immunohistochemistry with β‐amyloid (4G8), phosphorylated tau (AT8), p62, TDP‐43, α‐synuclein (81A), 68 kDa neurofilament (2F11), GFAP and CD68 antibodies were performed in selected sections to analyze the following areas: frontal cortex, temporal cortex, parietal cortex, occipital cortex, anterior cingulate cortex, hippocampus, amygdala, basal ganglia, thalamus, mesencephalon, pons, medulla oblongata, and cerebellum.
Result
Macroscopic evaluation of the brains showed considerable cortical gyrification. In addition, thick cortical ribbon was observed in the MRI. A complete neuropathological evaluation was available for two cases. Widespread β‐amyloid immunoreactivity was observed in the form of diffuse deposits, core‐space‐corona plaques, perivascular plaques, and amyloid angiopathy. A high frequency of classic neuritic plaques was observed. P‐tau antibody failed to label the dystrophic neurites. However, these lesions were revealed with p62 and neurofilament antibodies. Astrocyte hypertrophy surrounding plaques was observed without microglial activation. Very few hyperphosphorylated tau aggregates resembling neurofibrillary tangles and neuropil threads were found in the temporal and frontal cortex, and Lewy‐type and TDP‐43 pathology were not observed.
Conclusion
In summary, we found β‐amyloid immunoreactivity, classic neuritic plaques surrounded by astrocyte hypertrophy, but only rare P‐tau aggregates. To our knowledge, this is the first evidence reporting brain AD‐like alterations in capuchin monkeys which suggest that this species can be considered an advantageous animal model for AD research.