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

Abstract

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 Alzheimer’s 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. Aβ42 and Aβ40 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 – Aβ42/Aβ40 was negatively associated with gray matter thickness, and pTau217/Aβ42 (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 Alzheimer’s disease increase as chimpanzees age. We believe 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.