Neurodegenerative disease biomarkers Aβ(1–40), Aβ(1–42), tau, and p‐tau(181) in the vervet monkey cerebrospinal fluid: Relation to 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 Aβ(1–40), Aβ(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: Aβ(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 Aβ(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 Aβ(1–40) and p‐tau(181) as potentially valuable biomarkers of these processes.