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

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.