Characterization of cerebrospinal fluid biomarkers associated with neurodegenerative diseases in healthy cynomolgus and rhesus macaque monkeys

Abstract

Monkeys are becoming important translational models of neurodegenerative disease. To facilitate model development, we measured cerebrospinal fluid (CSF) concentrations of key biomarkers in healthy male and female cynomolgus and rhesus macaques. Amyloid beta (Aβ40, Aβ42), tau (total tau [t‐tau], phosphorylated tau [pThr181]), and neurofilament light (NfL) concentrations were measured in CSF of 82 laboratory‐housed, experimentally naïve cynomolgus (n = 33) and rhesus (n = 49) macaques. Aβ40 and Aβ42 were significantly higher in rhesus, and female rhesus were higher than males. NfL and t‐tau were higher in males, and NfL was higher in rhesus macaques. p‐tau was not affected by species or sex. We also examined whether sample location (lumbar or cisterna puncture) affected concentrations. Sample acquisition site only affected NfL, which was higher in CSF from lumbar puncture compared to cisterna magna puncture. Establishing normative biomarker values for laboratory‐housed macaque monkeys provides an important resource by which to compare to monkey models of neurodegenerative diseases.

Serum biomarkers associated with aging and neurodegeneration in common marmosets (Callithrix jacchus)

“…While marmosets are increasingly used in studies of aging and neurodegeneration, rhesus and cynomolgus macaques, and African green monkeys are more widely used. CSF concentrations of T-tau, P-tau, and NfL were not correlated with age in cynomolgus macaques ( Macaca fascicularis ) or rhesus macaques (( Macaca mulatta), though the age range tested in this study was relatively narrow (2—12 years) and did not capture aged animals [ 16 ]. However, Aβ concentration was significantly correlated with age in vervet monkeys ( Chlorocebus aethiops sabaeus )[ 4 ].…”

“…However, Aβ concentration was significantly correlated with age in vervet monkeys ( Chlorocebus aethiops sabaeus )[ 4 ]. Robertson et al[ 16 ] reported rhesus macaques had higher concentrations of Aβ40 and Aβ42 compared to cynomolgus macaques, and female rhesus had higher concentrations of Aβ40 and Aβ42 than male rhesus. Rizzo et al [ 15 ] reported increases in plasma Aβ42 and an increase in plasma Aβ42:40 ratio in genetically engineered marmosets with targeted AD gene knock-ins relative to wild type controls.…”