Neurodegenerative disease biomarkers Aβ1–40, Aβ1–42, tau, and p-tau181 in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy

Jason A. Chen, Scott C. Fears, Anna J. Jasinska, Alden Huang, Noor B. Al-Sharif, Kevin E. Scheibel, Thomas D. Dyer, Anne M. Fagan, John Blangero, Roger Woods, Matthew J. Jorgensen, Jay R. Kaplan, Nelson B. Freimer, Giovanni Coppola

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Abstract

Background: The Caribbean vervet monkey (Chlorocebus aethiops sabaeus) is a potentially valuable animal model of neurodegenerative disease. However, the trajectory of aging in vervets and its relationship to human disease is incompletely understood. Methods: To characterize biomarkers associated with neurodegeneration, we measured cerebrospinal fluid (CSF) concentrations of Aβ1–40, Aβ1–42, total tau, and p-tau181 in 329 members of a multigenerational pedigree. Linkage and genome-wide association were used to elucidate a genetic contribution to these traits. Results: Aβ1–40 concentrations were significantly correlated with age, brain total surface area, and gray matter thickness. Levels of p-tau181 were associated with cerebral volume and brain total surface area. Among the measured analytes, only CSF Aβ1–40 was heritable. No significant linkage (LOD > 3.3) was found, though suggestive linkage was highlighted on chromosomes 4 and 12. Genome-wide association identified a suggestive locus near the chromosome 4 linkage peak. Conclusions: Overall, these results support the vervet as a non-human primate model of amyloid-related neurodegeneration, such as Alzheimer's disease and cerebral amyloid angiopathy, and highlight Aβ1–40 and p-tau181 as potentially valuable biomarkers of these processes.

Original languageEnglish
Article numbere00903
JournalBrain and Behavior
Volume8
Issue number2
DOIs
StatePublished - Feb 1 2018

Keywords

  • Alzheimer's disease
  • amyloid beta
  • cerebral amyloid angiopathy
  • cerebrospinal fluid
  • tau
  • vervet

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    Chen, J. A., Fears, S. C., Jasinska, A. J., Huang, A., Al-Sharif, N. B., Scheibel, K. E., Dyer, T. D., Fagan, A. M., Blangero, J., Woods, R., Jorgensen, M. J., Kaplan, J. R., Freimer, N. B., & Coppola, G. (2018). Neurodegenerative disease biomarkers Aβ1–40, Aβ1–42, tau, and p-tau181 in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy. Brain and Behavior, 8(2), [e00903]. https://doi.org/10.1002/brb3.903