Chimpanzees share several age-related brain changes with humans, including reductions in neuron number and increases in neuropathology. Despite these parallels, there were previously no published studies examining peripheral biomarkers of Alzheimer's disease pathology in chimpanzees and how those biomarkers relate to age and to measures of cortical atrophy. This study aimed to evaluate clinically relevant serum biomarkers of pathological protein aggregation, neuroinflammation, and microglial function in chimpanzees (Pan troglodytes) and to test associations between these biomarkers, age, and structural brain phenotypes.
The authors measured multiple serum biomarkers tied to Alzheimer’s disease–relevant processes. They specifically report values for amyloid beta peptides Aβ42 and Aβ40, and for phosphorylated tau in the form pTau217, as well as markers reflecting neuroinflammation and microglial function. In addition to individual analytes, the study evaluated clinically meaningful biomarker ratios, including Aβ42/Aβ40 and pTau217/Aβ42 (reported for both total and brain-derived forms where applicable).
The manuscript reports a cross-sectional analysis of biomarker concentrations in serum and evaluates both cross-sectional differences and longitudinal changes. The study also examined relationships between biomarkers (and biomarker ratios) and quantitative measures of cortical morphology. The abstract indicates that analyses controlled for sex when assessing relationships with cortical measures. Specific procedural details (sample size, assay methods, imaging acquisition parameters, and statistical model specifications) are not provided in the abstract and therefore are not reported here; readers are referred to the full preprint and supplementary material for those methodological particulars.
Analyses identified both linear and quadratic relationships between age and several serum biomarkers and biomarker ratios. The general pattern reported is that most biomarkers increased with age in chimpanzees. The presence of quadratic relationships suggests some biomarkers may accelerate or change nonlinearly across the lifespan rather than following a simple straight-line increase.
When controlling for sex, age showed significant associations with multiple cortical morphological measures. Specifically, increasing age was associated with lower sulci surface area, shallower mean depth, and reduced gray matter thickness. Conversely, age was positively associated with fold opening, indicating altered cortical folding metrics with advancing age.
Higher serum levels of Aβ42 and Aβ40 were associated with cortical atrophy phenotypes: greater amyloid biomarker values corresponded to lower sulci surface area, reduced mean sulcal depth, and decreased gray matter thickness, as well as increased fold opening. These associations link peripheral amyloid-related measures to structural indicators of neurodegeneration in the chimpanzee brain.
The study evaluated clinically used biomarker ratios and their relationships with brain structure. The ratio Aβ42/Aβ40 was negatively associated with gray matter thickness. In contrast, pTau217/Aβ42 (reported both as total and as brain-derived) showed positive associations with surface area and gray matter thickness and a negative association with fold opening. These differential directions across ratios suggest that composite measures may relate to structural brain phenotypes in complex ways.
The reported findings are consistent with hypotheses derived from human Alzheimer’s disease research: many peripheral biomarkers associated with neurodegeneration and Alzheimer’s disease increase with age. The observed relationships between serum biomarkers and cortical atrophy phenotypes provide evidence that these clinically relevant measures track brain aging in nonhuman primates. The authors interpret these results as the first evidence linking peripheral Alzheimer’s biomarkers with brain-aging phenotypes in chimpanzees, underscoring the importance of chimpanzees as comparative models for aging and neurodegenerative disease research.
This report is a preprint and has not yet undergone peer review. The abstract summarizes primary findings but does not include detailed methodological parameters such as sample size, assay platforms, imaging protocols, or complete statistical model specifications; those details are reported in the full manuscript and supplementary material. Because the abstract does not provide these specifics, readers seeking to evaluate assay sensitivity, cohort composition, or longitudinal sampling intervals should consult the full preprint.
The authors declared no competing interests. Funders listed include the National Institutes of Health (grant numbers and program support are provided in the full record), Cattlemen for Cancer Research (Texas, US), and two PEPR programs (PEPR StratifyAging and PEPR PRODROM-ND). The work is posted on bioRxiv under a CC-BY 4.0 International license and remains a preprint at the time of posting.