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Plasma Amyloid Beta Concentrations in Aged and Cognitively Impaired Pet Dogs
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2020-09-24 , DOI: 10.1007/s12035-020-02140-9
Wojciech K Panek 1 , David M Murdoch 2 , Margaret E Gruen 1 , Freya M Mowat 1, 3 , Robert D Marek 2 , Natasha J Olby 1
Affiliation  

Longevity-associated neurological disorders have been observed across human and canine aging populations. Alzheimer’s disease (AD) and canine cognitive dysfunction syndrome (CDS) represent comparable diseases affecting both species as they age. Translational diagnostic and therapeutic research is needed for these incurable diseases. The amyloid β (Aβ) peptide family are AD-associated peptides with identical amino acid sequences between dogs and humans. Plasma Aβ42 concentration increases with age and decreases with AD in humans, and cerebrospinal fluid (CSF) concentration decreases in AD and correlates inversely with the amyloid load within the brain. Similarly, CSF Aβ42 concentrations decrease in dogs with CDS but there is limited and conflicting information on plasma Aβ42 concentrations in aging dogs and dogs with CDS. We measured plasma concentrations of Aβ42 and Aβ40 with an ultrasensitive single-molecule array assay (SIMOA) in a population of healthy aging dogs of different life stages (n = 36) and dogs affected with CDS (n = 11). In addition, the ratio of Aβ42/β40 was calculated. The mean plasma concentrations of Aβ42 and Aβ40 increased significantly with age (r2 = 0.27, p = 0.001; and r2 = 0.42, p < 0.001, respectively) and with life stage: puppy/junior group (0.43–2 years): 1.23 ± 0.95 and 38.26 ± 49.43 pg/mL; adult/mature group (2.1–9 years): 10.99 ± 5.45 and 131.05 ± 80.17 pg/mL; geriatric/senior group (9.3–14.5 years): 18.65 ± 16.65 and 192.88 ± 146.38 pg/mL, respectively. Concentrations of Aβ42 and Aβ40 in dogs with CDS (11.0–15.6 years) were significantly lower than age-matched healthy dogs at 11.61 ± 6.39 and 150.23 ± 98.2 pg/mL (p = 0.0048 and p = 0.001), respectively. Our findings suggest the dynamics of canine plasma amyloid concentrations are analogous to that found in aging humans with and without AD.



中文翻译:


老年和认知障碍宠物狗的血浆β淀粉样蛋白浓度



在人类和犬类老龄化群体中观察到与长寿相关的神经系统疾病。阿尔茨海默病(AD)和犬认知功能障碍综合征(CDS)是随着年龄增长而影响这两个物种的类似疾病。这些不治之症需要转化诊断和治疗研究。 β 淀粉样蛋白 (Aβ) 肽家族是 AD 相关肽,在狗和人类之间具有相同的氨基酸序列。在人类中,血浆 Aβ42 浓度随着年龄的增长而增加,并随着 AD 的增加而减少,而脑脊液 (CSF) 的浓度在 AD 中减少,并且与大脑内的淀粉样蛋白负荷成反比。同样,CDS 犬的 CSF Aβ42 浓度降低,但老年犬和 CDS 犬血浆 Aβ42 浓度的信息有限且相互矛盾。我们使用超灵敏单分子阵列测定法 ( SIMOA ) 测量了不同生命阶段的健康老龄狗 ( n = 36) 和患有 CDS 的狗 ( n = 11) 的血浆 Aβ42 和 Aβ40 浓度。另外,计算Aβ42/β40的比率。 Aβ42 和 Aβ40 的平均血浆浓度随着年龄的增长(分别为r 2 = 0.27, p = 0.001 ;和r 2 = 0.42, p < 0.001 )和生命阶段(幼犬/青少年组(0.43-2 岁))而显着增加:1.23±0.95 和 38.26±49.43 皮克/毫升;成人/成熟组(2.1-9岁):10.99±5.45和131.05±80.17pg/mL;老年/老年组(9.3-14.5岁):分别为18.65±16.65和192.88±146.38pg/mL。 CDS 犬(11.0-15.6 岁)的 Aβ42 和 Aβ40 浓度显着低于年龄匹配的健康犬,分别为 11.61 ± 6.39 和 150.23 ± 98。分别为 2 pg/mL( p = 0.0048p = 0.001 )。我们的研究结果表明,犬类血浆淀粉样蛋白浓度的动态变化与患有或不患有阿尔茨海默病的老年人中发现的相似。

更新日期:2020-09-24
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