Metabolic Biomarkers in Captive Olive Baboons (Papio anubis): Characterization and Relationships With Biomarkers of Neurodegeneration and Neuroinflammation.

Abstract

Diabetic patients are at an increased risk for neurodegeneration, neuroinflammation, and cognitive impairment, likely due to insulin dysregulation and subsequent hyperglycemia in the brain. This leads to cell apoptosis, amyloid beta accumulation, and tau hyperphosphorylation, all hallmarks of Alzheimer's disease and related dementias (ADRD). Baboons show neurological hallmarks of ADRD, including age-dependent tau pathology in neurons and glial cells, cerebral amyloid beta (Aβ) deposit-associated microvascular degeneration, and age-related increases in neurodegenerative and neuroinflammatory biomarkers. Here, we aim to characterize biomarkers of metabolic function according to age, sex, rearing, and obesity in captive olive baboons. We also examined associations between metabolic biomarkers (MBs) and biomarkers related to neurodegeneration (ND) and neuroinflammation (NI) (together, referred to NDNIBs) as well as between MBs and a behavioral indicator of aging and metabolic health (walking speed). We collected plasma in 133 baboons and cerebrospinal fluid (CSF) in 44 baboons, and recorded walking speeds in 128 baboons. For both NDNIB and MB, we calculated load scores using quartiles, and deviation scores using z-scores, where higher scores indicated higher biomarker levels and greater deviation from the mean, respectively. There were few significant differences across MBs as a function of age, sex, and rearing, and no differences as a function of obesity status. However, higher MB load scores were correlated with greater NDNIB deviation scores in CSF. Additionally, MB deviation scores predicted walking speeds. These data support previous studies showing that higher metabolic dysfunction is associated with greater concurrent burden of neurodegenerative indicators in nonhuman primates.