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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.

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

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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.

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