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Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs.
Molecular Neurobiology ( IF 5.1 ) Pub Date : 2020-05-30 , DOI: 10.1007/s12035-020-01951-0
Wojciech K Panek 1 , Margaret E Gruen 1 , David M Murdoch 2 , Robert D Marek 2 , Alexandra F Stachel 1 , Freya M Mowat 1, 3 , Korinn E Saker 1 , Natasha J Olby 1
Affiliation  

Age is a primary risk factor for multiple comorbidities including neurodegenerative diseases. Pet dogs and humans represent two populations that have experienced a significant increase in average life expectancy over the last century. A higher prevalence of age-related neurodegenerative diseases has been observed across both species, and human diseases, such as Alzheimer’s disease (AD) and amyotrophic lateral sclerosis (ALS), have canine analogs, canine cognitive dysfunction (CCD), and degenerative myelopathy (DM) respectively. In humans, protein biomarkers have proved useful in the prediction and diagnosis of neurodegeneration. Molecular signatures of many proteins are highly conserved across species. In this study, we explored the potential of the neuronal cytoskeletal protein neurofilament light chain (NfL) as a biomarker of neuro-aging in dogs using an ultrasensitive single-molecule array assay to measure plasma concentrations. Healthy dogs of different ages and dogs affected with CCD and DM were evaluated. The mean plasma NfL concentrations in the different age groups of the healthy population were as follows: 4.55 ± 1.70 pg/mL in puppy/junior group (0.43–2 years), 13.51 ± 6.8 pg/mL in adult/mature group (2.1–9 years), and 47.1 ± 12.68 pg/mL in geriatric/senior group (9.3–14.5 years). Concentrations in dogs with DM (7.5–12.6 years) and CCD (11.0–15.6 years) were 84.17 ± 53.57 pg/mL and 100.73 ± 83.72 pg/mL, respectively. Plasma NfL increases in an age-dependent manner and is significantly elevated in dogs diagnosed with neurodegenerative disease. This work identified plasma NfL as a key clinical index of neuro-aging and neurodegeneration in pet dogs. Our findings mirror recent reports from human neurodegenerative diseases.



中文翻译:

血浆神经丝轻链作为狗衰老和神经退行性变的生物标志物。

年龄是包括神经退行性疾病在内的多种合并症的主要危险因素。爱犬和人类代表着两个种群,在过去的一个世纪中,它们的平均预期寿命显着增加。在这两个物种中都发现了与年龄相关的神经退行性疾病的较高流行,人类疾病(例如阿尔茨海默氏病(AD)和肌萎缩性侧索硬化症(ALS))具有犬类类似物,犬类认知功能障碍(CCD)和变性性脊髓病( DM)。在人类中,蛋白质生物标记物已被证明可用于神经变性的预测和诊断。许多蛋白质的分子标记在物种间高度保守。在这个研究中,我们探索了神经元细胞骨架蛋白神经丝轻链(NfL)作为狗中神经衰老的生物标志物的潜力,使用超灵敏单分子阵列测定法测量血浆浓度。评价了不同年龄的健康犬和受CCD和DM影响的犬。健康人群不同年龄组的平均血浆NfL浓度如下:幼犬/初中组(0.43-2岁)4.55±1.70 pg / mL,成年/成年组13.51±6.8 pg / mL(2.1- 9岁),老年/老年组(9.3–14.5岁)为47.1±12.68 pg / mL。DM(7.5–12.6岁)和CCD(11.0–15.6岁)犬的浓度分别为84.17±53.57 pg / mL和100.73±83.72 pg / mL。在诊断为神经退行性疾病的狗中,血浆NfL随年龄增长而增加。这项工作确定血浆NfL是宠物狗神经衰老和神经变性的关键临床指标。我们的发现反映了人类神经退行性疾病的最新报道。

更新日期:2020-06-26
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