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

Product:

CNS Disease Panel 120

Topic:

Neurology

Disease Area:

Alzheimer's Disease

Sample Type:

Chimpanzee Serum

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.

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Authors and Affiliations

Michele M. Mulholland¹*, Elizabeth R. Magden¹, Angela M. Achorn², Jean-Francois Mangin³, and William D. Hopkins¹

¹ Department of Comparative Medicine, Michale E Keeling Center for Comparative Medicine and Research, MD Anderson Cancer Center, Bastrop, Texas 78602, USA
² Department of Anthropology, University of Texas at Rio Grande Valley, Edinburg, Texas
³ Université Paris-Saclay, CEA, CNRS, Neurospin, Baobab, Gif-sur-Yvette, Paris, France

* Corresponding author: Michele M. Mulholland

Steve Williams, MD, PhD

CSO

Dr. Willams serves as the company’s Chief Scientific Officer. He was previously Chief Medical Officer at Standard Biotools and at SomaLogic where he pioneered the discipline for discovery and validation of predictive, diagnostic and prognostic models using machine-learning applied to large-plex proteomics. 20 such tests were used for drug characterization, safety and efficacy when incorporated in clinical drug trials at Pharma/Biotech and 17 different multivariate tests were validated and translated into regulated healthcare uses. Prior to SomaLogic, Dr. Williams was at Pfizer in the UK and the USA as a clinical triallist in Translational Medicine, and subsequently as VP, Global Clinical Technology. He sat on the National Advisory Council for the National Institute of Biomedical Imaging and Bioengineering, the Executive Committee for the FNIH Biomarkers Consortium, and worked with FDA and PhRMA on developing evidentiary standards for biomarker qualification. Dr. William’s medical training was in London, at Charing Cross and Westminster Medical School, followed by a PhD in medicine/physiology at the same institution and training in Radiology at the University of Newcastle Upon Tyne. Steve is co-inventor on 26 proteomics patents and author/coauthor on multiple foundational proteomics manuscripts.

Justin McAnear

CFO

Mr. McAnear serves as the company’s Chief Financial Officer. He brings over 25 years of operational and financial leadership experience across various sectors and was instrumental in taking 10x Genomics public in 2019, serving as its CFO for over five years. Mr. McAnear served for over 3 years as Tesla’s VP of Worldwide Finance and Operations, supporting landmark initiatives such as the Model X and Model 3 launches and Solar City acquisition. He also held various roles at Apple and J&J earlier in his career and served as a naval officer and aviator for over 9 years.