Neurodegenerative disease biomarkers Aβ
| Autor: | Jason A, Chen, Scott C, Fears, Anna J, Jasinska, Alden, Huang, Noor B, Al-Sharif, Kevin E, Scheibel, Thomas D, Dyer, Anne M, Fagan, John, Blangero, Roger, Woods, Matthew J, Jorgensen, Jay R, Kaplan, Nelson B, Freimer, Giovanni, Coppola |
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| Rok vydání: | 2017 |
| Předmět: |
Male
Aging Genetic Linkage Neuroimaging tau Proteins cerebrospinal fluid vervet Alzheimer Disease Chlorocebus aethiops Animals tau cerebral amyloid angiopathy Original Research Amyloid beta-Peptides Monkey Diseases Brain Neurodegenerative Diseases Organ Size Alzheimer's disease Chromosomes Mammalian Peptide Fragments Pedigree amyloid beta Models Animal Female Biomarkers Genome-Wide Association Study |
| Zdroj: | Brain and Behavior |
| ISSN: | 2162-3279 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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