Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs.

Plasma Neurofilament Light Chain as a Translational Biomarker of Aging and Neurodegeneration in Dogs.
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DOI:
10.1007/s12035-020-01951-0
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发表时间:
2020-07
影响因子:
5.1
通讯作者:
Olby NJ
Olby NJ
中科院分区:
医学2区
文献类型:
--
作者:
Panek WK;Gruen ME;Murdoch DM;Marek RD;Stachel AF;Mowat FM;Saker KE;Olby NJ

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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。宠物狗和人类代表着过去一百年来平均预期寿命显着增长的两个群体。在各个物种和人类疾病中,与年龄相关的神经退行性疾病的患病率均较高,例如阿尔茨海默氏病 (AD) 和肌萎缩侧索硬化症 (ALS),在犬类中也有类似疾病,即犬认知功能障碍 (CCD) 和退行性脊髓病 (DM)。在人类中,蛋白质生物标志物已被证明可用于预测和诊断神经退行性疾病。许多蛋白质的分子特征在物种间高度保守。在这项研究中,我们使用超灵敏单分子阵列测定法来测量血浆浓度,探讨了神经元细胞骨架蛋白神经丝轻链(NfL)作为狗神经衰老生物标志物的潜力。对不同年龄的健康狗以及患有 CCD 和 DM 的狗进行了评估。健康人群不同年龄组的平均血浆NfL浓度为:幼犬/青少年组(0.43-2岁)为4.55±1.70 pg/mL,成年/成年组(2.1-9岁)为13.51±6.8 pg/mL,老年/老年组为47.1±12.68 pg/mL(9.3-14.5岁)。年)。患有 DM(7.5-12.6 岁)和 CCD(11.0-15.6 岁)狗的浓度分别为 84.17±53.57 pg/mL 和 100.73±83.72 pg/mL。血浆 NfL 以年龄依赖性方式增加,并且在诊断患有神经退行性疾病的狗中显着升高。这项工作将血浆 NfL 确定为宠物狗神经衰老和神经退行性变的关键临床指标。我们的发现反映了人类神经退行性疾病的最新报告。
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 hundred years. 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 analogues, 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: 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.
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