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Biology subjects

Magden, E. R.

Publications and source records attributed to Magden, E. R..

3 recordsLinked to original sources

Clinically Relevant Biomarkers of Alzheimers Disease Are Associated with Age and Cortical Atrophy in Chimpanzees (Pan troglodytes)

Chimpanzees share a number of age-related brain changes with humans, such as reductions in neurons and increases in neuropathology. To date, there are no published studies of peripheral biomarkers related to Alzheimers pathology and their associations with age and cortical atrophy in chimpanzees. Here we examined cross-sectional differences and longitudinal changes in biomarkers of pathological protein aggregation, neuroinflammation, and microglial function measured in serum. We examined the relationships between biomarkers and clinically relevant biomarker ratios with both age and cortical atrophy. We found linear and quadratic relationships between age and several biomarkers and ratios. Most biomarkers increased with age. While controlling for sex, we found significant negative associations between age and sulci surface area, mean depth, and gray matter thickness and a positive association with fold opening. A{beta}42 and A{beta}40 showed higher biomarker values associated with lower surface area, mean depth, and gray matter thickness and higher fold opening values. The clinically relevant biomarker ratios were also associated with cortical atrophy - A{beta}42/A{beta}40 was negatively associated with gray matter thickness, and pTau217/A{beta}42 (both total and brain-derived) was positively associated with surface area and gray matter thickness and negatively associated with fold opening. Consistent with our hypotheses and previous findings in humans, many peripheral biomarkers associated with neurodegeneration and Alzheimers disease increase as chimpanzees age. We believe this is the first evidence demonstrating an association between these clinically relevant biomarkers of Alzheimers disease and phenotypes of brain aging in nonhuman primates, underscoring their importance as models of aging and neurodegenerative disease.

neuroscience↗

A Comparative Study of Plasma Biomarkers of Neurodegeneration in Rhesus Monkeys (Macaca mulatta) and Baboons (Papio anubis)

Many nonhuman primate species recapitulate the neuropathological features of sporadic Alzheimers 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 A{beta}42/A{beta}40 ratio than baboons. Finally, in both species, lower A{beta}42/A{beta}40 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.

neuroscience↗

Comparative analysis of cellular immune responses in conventional and SPF Baboons (Papio spp.)

Baboons (papio spp.) have served as a successful model of human disease such as cardiac and respiratory, infectious, diabetes, genetics, immunology, aging, and xenotransplantation. The development of an immunologically defined specific-pathogen free (SPF) baboon model has further advanced research, especially with studies involving the immune system and immunosuppression. In this study, we compare normal immunological changes of peripheral blood mononuclear cell (PBMC) subsets, and their function in age-matched conventional and SPF baboons. Our results demonstrate that both groups have comparable numbers of different lymphocyte subsets, but there are phenotypic differences in central and effector memory T cells subsets that are more pronounced in the CD4+ T cells. Despite equal proportions of CD3+ T cells among the conventional and SPF baboon groups, PBMC show higher proliferative responses to mitogens PHA and PWM and higher IFN-{gamma} producing cells to Con A and PWM in the conventional group. Plasma levels of the inflammatory cytokine TNF- were significantly higher in SPF baboons. Exposure of PBMC from conventional baboons to various Toll like ligands (TLR ligands) TLR-3, TLR-4 and TLR-8 show higher IFN-{gamma} producing cells while PBMC from SPF baboons stimulated with TLR-5 and TLR-6 ligand show higher IFN-{gamma} producing cells. These findings suggest that while the lymphocyte subsets in conventional and SPF baboons share many phenotypic and functional similarities, specific differences exist in immune function of lymphocytes which could impact the quality and quantity of innate and adaptive immune responses. These differences should be considered for better experimental outcomes, specifically in studies measuring immunological endpoints.

immunology↗