Age-associated changes in amyloid-β and formaldehyde concentrations in cerebrospinal fluid of rhesus monkeys.

Zhen-Hui Li,中国科学院昆明动物研究所中国科学院/云南省动物模型与人类疾病重点实验室，云南 昆明 650223，中国 ,中国科学院生物物理研究所脑与认知科学国家重点实验室，北京 100101，中国 ,Rong-Qiao He,中国科学院昆明灵长类研究中心/模式动物表型与遗传研究国家重大科技基础设施（灵长类设施），云南 昆明 650223，中国 ,Xin-Tian Hu,中国科学院脑卓越中心，上海 200031，中国 ,大理大学基础医学科学院，云南 大理 671000，中国 , ,Xia-Ping He,中国科学院大学昆明生命科学学院，云南 昆明 650204，中国 ,Hao Li

doi:10.24272/j.issn.2095-8137.2020.088

Zhen-Hui Li, 中国科学院昆明动物研究所中国科学院/云南省动物模型与人类疾病重点实验室，云南昆明 650223，中国 + Show 10 more

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https://doi.org/10.24272/j.issn.2095-8137.2020.088

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Abstract

Rhesus monkeys ( Macaca mulatta) are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans (Zhang et al., 2014). Rhesus monkeys also display similar hallmarks of aging and neurodegeneration as humans, including formation of senile plaques in the brain (Beckman et al., 2019; Paspalas et al., 2018). However, changes in formaldehyde (FA) levels in the cerebrospinal fluid (CSF) of rhesus monkeys with aging have not been reported. Additionally, whether changes in CSF FA are correlated with changes in amyloid-β (Aβ) concentrations have not yet been explored. Here, the CSF levels of Aβ 40, Aβ 42, and FA were measured in 56 rhesus monkeys of different ages, ranging from 4 to 26 years old. Results revealed significant declines in Aβ 40 and Aβ 42, and an increase in FA with age. Interestingly, the increase in FA levels was negatively correlated with Aβ 40 and Aβ 42 concentrations in aged rhesus monkeys but not in young and middle-aged monkeys. These results appear to parallel changes seen within human aging, i.e., decreased levels of CSF Aβ and increased levels of FA in normal aged adults and Alzheimer's disease (AD) patients. These findings further indicate that rhesus monkeys are a reliable model for studying age-related neurological disorders such as AD and suggest that FA is an important factor in AD development and may be used as a diagnostic indicator of such disease.

Highlights

Rhesus monkeys (Macaca mulatta) are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans (Zhang et al, 2014)
In non-human primate (NHP) studies, elevated FA levels lead to impaired memory, and to the occurrence of all the pathological hallmarks of human Alzheimer’s disease (AD) in the brain, including senile plaques, neurofibrillary tangles, neuronal loss, and glial proliferation (Yang et al, 2014b; Zhai et al, 2018)
No study has investigated the relationship of FA concentrations in cerebrospinal fluid (CSF) samples from different aged rhesus monkeys or the correlation between FA and Aβ levels in CSF samples

Summary

Introduction

Rhesus monkeys (Macaca mulatta) are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans (Zhang et al, 2014). Several studies have found that FA concentration in the human body increases with age, and concentrations of FA in urine, blood, CSF, and brain tissue of AD patients are significantly higher than those in the control group at the same age (He et al, 2010; Tong et al, 2013). In non-human primate (NHP) studies, elevated FA levels lead to impaired memory, and to the occurrence of all the pathological hallmarks of human AD in the brain, including senile plaques, neurofibrillary tangles, neuronal loss, and glial proliferation (Yang et al, 2014b; Zhai et al, 2018).

Results

Conclusion