Previous studies of aging cynomolgus monkeys from our group identified spontaneous age-associated cognitive declines associated with biomarkers and brain lesions reminiscent of Alzheimer's Disease (AD), in a proportion of aged monkeys. However, the molecular mechanisms that underlie the spontaneous amyloid disorders and cognitive declines observed in these affected monkeys have yet to be investigated in detail. Using reverse transcriptase quantitative real time PCR techniques, normalized to the ACTB housekeeping gene, we analyzed the expression patterns of a number of genes which have been implicated in amyloid and tau abnormalities, in well-characterized aged cynomolgus monkeys with cognitive decline. A significantly increased expression of the genes coding for glyceraldehyde 3-phosphate dehydrogenase (GAPDH), was found in aged-cognitive decline monkeys compared to age-matched healthy controls. GAPDH has been implicated in several neurodegenerative diseases and interacts with beta amyloid precursor proteins. These findings provide support for the utilization of cynomolgus macaques in translational preclinical research as valid spontaneous models in experimental investigations of the relationships among aging, cognitive decline, and the neuropathy of AD.

中文翻译：

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食蟹猴中 GAPDH 的表达增加，伴有自发性认知能力下降和淀粉样病变，让人联想到阿尔茨海默氏症型疾病，这反映在循环中

我们小组先前对衰老食蟹猴的研究发现，在一定比例的老年猴子中，与生物标志物和脑损伤相关的自发性年龄相关认知下降与阿尔茨海默病 (AD) 相关。然而，在这些受影响的猴子中观察到的自发性淀粉样蛋白紊乱和认知下降的分子机制尚待详细研究。使用逆转录酶定量实时 PCR 技术，标准化为ACTB管家基因，我们分析了一些基因的表达模式，这些基因与淀粉样蛋白和 tau 异常有关，在具有良好特征的老年食蟹猴中具有认知能力下降。与年龄匹配的健康对照组相比，在老年认知能力下降的猴子中发现编码甘油醛 3-磷酸脱氢酶 (GAPDH) 的基因的表达显着增加。GAPDH 与几种神经退行性疾病有关，并与β淀粉样蛋白前体蛋白相互作用。这些发现为在转化临床前研究中使用食蟹猴作为有效自发模型在衰老、认知衰退和 AD 神经病变之间关系的实验研究中的应用提供了支持。