@article{11050826981f4c8ea5740eadd6954e31,
title = "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",
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.",
keywords = "Alzheimer's disease, amyloid beta, cerebral amyloid angiopathy, cerebrospinal fluid, tau, vervet",
author = "Chen, {Jason A.} and Fears, {Scott C.} and Jasinska, {Anna J.} and Alden Huang and Al-Sharif, {Noor B.} and Scheibel, {Kevin E.} and Dyer, {Thomas D.} and Fagan, {Anne M.} and John Blangero and Roger Woods and Jorgensen, {Matthew J.} and Kaplan, {Jay R.} and Freimer, {Nelson B.} and Giovanni Coppola",
note = "Funding Information: This work was supported by the Tau Consortium to GC, the National Institutes of Health (F31 NS084556 to JAC and P01 AG026276 to AMF, PI: JC Morris). We acknowledge the support of the NINDS Informatics Center for Neurogenetics and Neurogenomics (P30 NS062691) and the Vervet Research Colony (P40 RR019963/OD010965 and the Wake Forest School of Medicine). JAC is a founder of Verge Genomics and holds an equity stake in the company. AMF is a member of the Scientific Advisory Boards of AbbVie, IBL International, and Roche and provides consultation for DiamiR and LabCorp The authors thank Susan Service for assistance with genetic analyses, Aarti Shah for assistance with the CSF analyte measurements, and the staff of the Vervet Research Colony for the collection of CSF samples. Funding Information: This work was supported by the Tau Consortium to GC, the National Institutes of Health (F31 NS084556 to JAC and P01 AG026276 to AMF, PI: JC Morris). We acknowledge the support of the NINDS Informatics Center for Neurogenetics and Neurogenomics (P30 NS062691) and the Vervet Research Colony (P40 RR019963/ OD010965 and the Wake Forest School of Medicine). JAC is a founder of Verge Genomics and holds an equity stake in the company. AMF is a member of the Scientific Advisory Boards of AbbVie, IBL International, and Roche and provides consultation for DiamiR and LabCorp Publisher Copyright: {\textcopyright} 2018 The Authors. Brain and Behavior published by Wiley Periodicals, Inc.",
year = "2018",
month = feb,
day = "1",
doi = "10.1002/brb3.903",
language = "English (US)",
volume = "8",
journal = "Brain and Behavior",
issn = "2157-9032",
publisher = "John Wiley and Sons Inc.",
number = "2",
}