Age-associated changes in amyloid-β and formaldehyde concentrations in cerebrospinal fluid of rhesus monkeys
Zhenhui 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, Xiaping He, Hao Li, Rongqiao He, Xintian Hu, 中国科学院大学昆明生命科学学院，云南 昆明 650204，中国, 大理大学基础医学科学院，云南 大理 671000，中国, 中国科学院脑卓越中心，上海 200031，中国, 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, 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
Abstract
Rhesus monkeys (<i>Macaca mulatta</i>) are valuable experimental animals for studies on neurodegenerative diseases due to their evolutionarily close relationship to humans (<xref ref-type="bibr" rid="bZhang2014">Zhang et al., 2014</xref>). Rhesus monkeys also display similar hallmarks of aging and neurodegeneration as humans, including formation of senile plaques in the brain (<xref ref-type="bibr" rid="bBeckman2019">Beckman et al., 2019</xref>; <xref ref-type="bibr" rid="bPaspalas2018">Paspalas et al., 2018</xref>). 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<sub>40</sub>, Aβ<sub>42</sub>, and FA were measured in 56 rhesus monkeys of different ages, ranging from 4 to 26 years old. Results revealed significant declines in Aβ<sub>40</sub> and Aβ<sub>42</sub>, and an increase in FA with age. Interestingly, the increase in FA levels was negatively correlated with Aβ<sub>40</sub> and Aβ<sub>42</sub> 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.