Journal
BRAIN AND BEHAVIOR
Volume 8, Issue 2, Pages -Publisher
WILEY
DOI: 10.1002/brb3.903
Keywords
Alzheimer's disease; amyloid beta; cerebral amyloid angiopathy; cerebrospinal fluid; tau; vervet
Categories
Funding
- Tau Consortium
- National Institutes of Health [F31 NS084556, P01 AG026276]
- NINDS Informatics Center for Neurogenetics and Neurogenomics [P30 NS062691]
- Vervet Research Colony [P40 RR019963/OD010965]
- Vervet Research Colony (Wake Forest School of Medicine)
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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 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.
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