Comparison of cerebrospinal fluid biomarkers relevant to neurodegenerative diseases in healthy cynomolgus and rhesus macaque monkeys

Abstract

Structured AbstractO_ST_ABSINTRODUCTIONC_ST_ABSNon-human primates are important translational models of neurodegenerative disease. We characterized how species, sex, age, and site of sampling affected concentrations of key biomarkers of neurodegeneration. METHODSAmyloid-beta (A{beta}40, A{beta}42), tau (tTau, pTau), and neurofilament light (NFL) in CSF were measured in 82 laboratory-housed naive cynomolgus and rhesus macaques of both sexes. RESULTSA{beta}40, A{beta}42, and NFL were significantly higher in rhesus compared with cynomolgus macaques. tTau and NFL were higher in males. pTau was not affected by species or sex. Site of acquisition only affected NFL, with NFL being higher in CSF acquired from lumbar compared with cisterna magna puncture. DISCUSSIONNormative values for key neurodegeneration biomarkers were established for laboratory housed cynomolgus and rhesus macaque monkeys. Differences were observed as a function of species, sex and site of CSF acquisition that should be considered when employing primate models. Research In ContextO_LISystematic review: We reviewed reports characterizing CSF biomarkers of neurodegenerative diseases in non-human primates - an increasingly important model of disease - revealing that studies with laboratory housed macaque monkeys were of small sample size, with a paucity of data about how biomarkers varied as a function of species, sex, age, and site of acquisition. C_LIO_LIInterpretation: To address this gap, we collected CSF from 82 naive laboratory housed male and female macaques of two species and measured A{beta}40, A{beta}42, tTau, pTau, and NFL. In addition to providing normative statistics for concentrations of these biomarkers, we revealed various species and sex differences. C_LIO_LIFuture directions: Establishing normative values of biomarkers is an important step to the efficient development of cynomolgus and rhesus macaques as models of neurodegenerative disorders such as Alzheimers disease. Reference values reduce the need for large control groups by which to compare with disease model animals. C_LI