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

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 A beta(1-40), A beta(1-42), total tau, and p-tau(181) in 329 members of a multigenerational pedigree. Linkage and genome-wide association were used to elucidate a genetic contribution to these traits. Results: A beta(1-40) concentrations were significantly correlated with age, brain total surface area, and gray matter thickness. Levels of p-tau(181) were associated with cerebral volume and brain total surface area. Among the measured analytes, only CSF A beta(1-40) 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 A beta(1-40) and p-tau(181) as potentially valuable biomarkers of these processes.