Open AccessNeurodegenerative 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
Author(s) -
Chen Jason A.,
Fears Scott C.,
Jasinska Anna J.,
Huang Alden,
AlSharif 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
Publication year - 2018
Publication title -
brain and behavior
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.915
H-Index - 41
ISSN - 2162-3279
DOI - 10.1002/brb3.903
Subject(s) - neurodegeneration , vervet monkey , cerebrospinal fluid , biology , alzheimer's disease , locus (genetics) , disease , pathology , genetics , neuroscience , medicine , gene , evolutionary biology
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.