Neurodegenerative disease biomarkers Aβ1-40, Aβ1-42, tau, and p-tau181in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy
| Autor: | Thomas D. Dyer, Scott C Fears, Anne M. Fagan, Anna J. Jasinska, Roger P. Woods, Matthew J. Jorgensen, Giovanni Coppola, Nelson B. Freimer, Kevin E Scheibel, Jason A. Chen, Alden Y. Huang, Jay R. Kaplan, Noor B Al-Sharif, John Blangero |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty biology Amyloid beta Neurodegeneration Locus (genetics) Disease biology.organism_classification medicine.disease 03 medical and health sciences Behavioral Neuroscience 030104 developmental biology 0302 clinical medicine Cerebrospinal fluid Endocrinology Chromosome 4 Internal medicine medicine biology.protein Vervet monkey Cerebral amyloid angiopathy 030217 neurology & neurosurgery |
| Zdroj: | Brain and Behavior. 8:e00903 |
| ISSN: | 2162-3279 |
| Popis: | Author(s): Chen, Jason A; Fears, Scott C; Jasinska, Anna J; Huang, Alden; Al-Sharif, 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 | 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 g 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. |
| Databáze: | OpenAIRE |
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