Introduction
Neurofilament light (NFL) in cerebrospinal fluid (CSF) is elevated in neurodegenerative disease patients, and may track disease progression and treatment. Macaque monkeys are emerging as important translational models of neurodegeneration, and NFL may be a useful biomarker.
Methods
To determine the influence of a previous lumbar puncture (LP) on NFL, we collected CSF at multiple time points in macaque monkeys via LP or cisterna magna puncture. NFL, amyloid beta (Aβ40, Aβ42), and tau (tTau, pTau) in CSF were measured by standard enzyme‐linked immunosorbent assay and multiplex.
Results
NFL was significantly elevated at 14 to 23 days after an LP (median increase: 162%). Aβ and tau biomarkers remained stable. NFL peaked and decayed over 1 to 2 months after LP. NFL was not elevated after cisterna magna puncture.
Discussion
Results suggest damage of the cauda equina during LP may increase NFL. Caution should be taken in interpreting NFL concentration in studies in which repeat LPs are performed.
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.
Neurophysiologic studies of NHP commonly involve their transfer from a housing enclosure to a laboratory by using a mobile chair. This transfer should be performed in a manner that is safe and minimizes stress for both animal and handler. The risk of harm associated with attempting to transfer these animals is increased when they are mature and naïve. We have modified previous chair designs and transfer methodologies to reduce this risk by maintaining a constant barrier between NHP and handler while providing control to the handler to facilitate chairing. Chair modifications were built inhouse, and a commercial, hydraulic lift table was used to dock the primate chair to home cages of different heights. The docking chair method was used with 8 adult, male rhesus macaques. A graduate student transferred the animals without complications. These modifications did not compromise existing features of the chair, they did not require training time in addition to that for the standard chairing method in our facility, and they improved safety. These refinements to a commonly used chair and transfer methodology support rapid habituation, safe transfer and reduced stress for both animal and handler. The refinements we describe mitigate the potential risk of harm during NHP transfers and thus advance animal welfare.
INTRODUCTION: Non-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.
METHODS: Amyloid-beta (Aβ40, Aβ42), tau (tTau, pTau), and neurofilament light (NFL) in CSF were measured in 82 laboratory-housed naive cynomolgus and rhesus macaques of both sexes.
RESULTS: Aβ40, Aβ42, 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.
DISCUSSION: Normative 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.
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