In light of the evidence that nonhuman primates naturally develop Alzheimer's disease neuropathologies, there is a renewed interest in research on the comparative biology of aging, including neurological changes across the age groups in species with diverse lifespans. In this paper, we examined age‐related differences in two measures of cortical folding, mean depth and fold opening, in a sample of chimpanzees (Pan troglodytes) and olive baboons (Papio anubis). We found significant species differences in the slope and pattern of age‐related changes in cortical folding. As predicted, chimpanzees showed negative linear associations between age and mean depth and positive linear associations between age and fold opening, as we see in humans. However, contrary to our hypotheses, baboons showed positive quadratic associations between age and mean depth and negative quadratic associations between age and fold opening. Additionally, within the baboons but not the chimpanzees, significant sex differences were found in age‐related differences in cortical folding. Here, male baboons showed significant linear associations between age, sulci depth, and fold opening, much like male and female chimpanzees. However, for female baboons, slopes of age‐related differences in fold opening were flat or showed slight quadratic associations. It is possible that variation in primate social systems and/or reproductive aging may influence sex and species differences in brain aging. Longitudinal studies on primate brain aging, as well as comparative research with additional taxa, could shed light on the causes and implications of these differences.
William D Hopkins, Angela M. Achorn, M. M. Mulholland et al.· American Journal of Primatol...· 0 citations
Many nonhuman primate species recapitulate the neuropathological features of sporadic Alzheimer’s disease (AD) to varying degrees. As with humans, the assessment of AD-related pathology in nonhuman primates has historically relied on the use of postmortem brain tissues. In vivo alternatives, such as PET imaging tracers and fluid biomarkers, have been developed for use in humans but require further validation in nonhuman primates before replacing postmortem analyses. Here we employed the Nucleic Acid-Linked Immuno-Sandwich Assay (NULISATM) CNS Disease panel to compare age-related changes in plasma biomarkers in two nonhuman primate species (rhesus monkeys and baboons). In addition, we examined whether amyloid and tau biomarkers were associated with brain atrophy, as measured by gray matter volume. We found significant associations between age and multiple biomarkers of neurodegeneration for both species, as well as significant differences in the patterns of these associations between the two species. For the phosphorylated tau measures, though rhesus monkeys had higher values, baboons showed significant and stronger associations with age. By contrast, rhesus monkeys exhibited an earlier age-related decline in Aβ42/Aβ40 ratio than baboons. Finally, in both species, lower Aβ42/Aβ40 ratios were associated with lower gray matter volumes. This is the first systematic comparative study of age-related changes in neurodegeneration biomarkers in two closely related nonhuman primates using comparable age ranges and sample sizes, and the same multiplex assay. Future studies should examine longitudinal changes in these biomarkers as well as validate the plasma findings using cerebral spinal fluid.
M. M. Mulholland, Elizabeth R. Magden, H. Scholtzova et al.· bioRxiv· 0 citations
This work believes this is the first evidence demonstrating an association between these clinically relevant biomarkers of Alzheimer’s disease and phenotypes of brain aging in nonhuman primates, underscoring their importance as models of aging and neurodegenerative disease.
M. Mulholland, Elizabeth R. Magden, Angela M. Achorn et al.· bioRxiv· 0 citations