神经退行性疾病生物标志物 Aβ、Aβ、tau 和 p-tau 在非洲绿猴脑脊液中的变化：与正常衰老、遗传影响和脑淀粉样血管病的关系。
Neurodegenerative disease biomarkers Aβ, Aβ, tau, and p-tau in the vervet monkey cerebrospinal fluid: Relation to normal aging, genetic influences, and cerebral amyloid angiopathy.
机构信息
Department of Psychiatry The Jane and Terry Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California Los Angeles CA USA.
Interdepartmental Program in Bioinformatics University of California Los Angeles CA USA.
出版信息
Brain Behav. 2018 Jan 13;8(2):e00903. doi: 10.1002/brb3.903. eCollection 2018 Feb.
BACKGROUND
The Caribbean vervet monkey () 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, Aβ, total tau, and p-tau in 329 members of a multigenerational pedigree. Linkage and genome-wide association were used to elucidate a genetic contribution to these traits.
RESULTS
Aβ concentrations were significantly correlated with age, brain total surface area, and gray matter thickness. Levels of p-tau were associated with cerebral volume and brain total surface area. Among the measured analytes, only CSF Aβ 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 and p-tau as potentially valuable biomarkers of these processes.
背景
加勒比猕猴（）是一种具有潜在价值的神经退行性疾病动物模型。然而，关于其衰老轨迹及其与人类疾病的关系尚不完全清楚。
方法
为了研究与神经退行性变相关的生物标志物，我们对一个多世代家系的 329 名成员的脑脊液（CSF）中的 Aβ、Aβ、总 tau 和 p-tau 浓度进行了测量。采用连锁分析和全基因组关联分析来阐明这些特征的遗传贡献。
结果
Aβ 浓度与年龄、脑总表面积和灰质厚度显著相关。p-tau 水平与脑容量和脑总表面积相关。在所测量的分析物中，只有 CSF Aβ 是可遗传的。尽管在染色体 4 和 12 上突出了提示性连锁（LOD>3.3），但未发现显著的连锁（LOD>3.3）。全基因组关联分析鉴定出染色体 4 连锁峰附近的一个提示性基因座。
结论
总体而言，这些结果支持猕猴作为与淀粉样蛋白相关的神经退行性变（如阿尔茨海默病和脑淀粉样血管病）的非人类灵长类动物模型，并突出了 Aβ 和 p-tau 作为这些过程的潜在有价值的生物标志物。
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