Department of Biotechnology and Animal Science, College of Bioresources, National Ilan University, Yilan City, Taiwan.
Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan.
PLoS One. 2020 May 29;15(5):e0233289. doi: 10.1371/journal.pone.0233289. eCollection 2020.
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by two aggregates, namely, amyloid-β (Aβ) plaques and neurofibrillary tangles (NFTs) of hyperphosphorylated tau protein (tau-p), which are released into the blood in a very small amount and cannot be easily detected. An increasing number of recent studies have suggested that S-glutathionylated glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is highly correlated with Aβ in patients with AD and that S-glutathionylated GAPDH plays a role as a proapoptotic factor in AD. We found that S-glutathionylated GAPDH is abundant in the blood of AD patients, which is unusual because S-glutathionylated GAPDH cannot exist in the blood under normal conditions. The aim of this study was to further explore the correlation between the S-glutathionylated GAPDH levels in blood plasma and AD progression. As controls, we recruited 191 people without AD, which included 111 healthy individuals and 37 patients with depression and insomnia, in the psychosomatic clinic. Moreover, 47 patients with AD (aged 40-89 years) were recruited at the neurology clinic. The blood S-glutathionylated GAPDH levels in the AD patients were significantly (p < 0.001) higher (752.7 ± 301.7 ng/dL) than those in the controls (59.92 ± 122.4 ng/dL), irrespective of gender and age. For AD diagnosis, the criterion blood S-glutathionylated GAPDH level > 251.62 ng/dL exhibited 95.74% sensitivity and 92.67% specificity. In fact, the individuals aged 70-89 years, namely, 37 patients from the psychosomatic clinic and 42 healthy individuals, showed significant blood S-glutathionylated GAPDH levels (230.5 ± 79.3 and 8.05 ± 20.51 ng/dL, respectively). This finding might indicate neurodegenerative AD progression in psychosomatic patients and suggests that the degree of neuronal apoptosis during AD progression might be sensitively evaluated based on the level of S-glutathionylated GAPDH in blood.
阿尔茨海默病（AD）是一种进行性神经退行性疾病，其特征为两种聚集物，即淀粉样β（Aβ）斑块和过度磷酸化 tau 蛋白（tau-p）的神经原纤维缠结（NFT），它们会以非常少量的形式释放到血液中，并且难以被轻易检测到。越来越多的最近研究表明，S-谷胱甘肽化甘油醛 3-磷酸脱氢酶（GAPDH）与 AD 患者中的 Aβ高度相关，并且 S-谷胱甘肽化 GAPDH 作为 AD 中的促凋亡因子发挥作用。我们发现，S-谷胱甘肽化 GAPDH 在 AD 患者的血液中含量丰富，这很不寻常，因为在正常条件下，S-谷胱甘肽化 GAPDH 不能存在于血液中。本研究的目的是进一步探讨血浆中 S-谷胱甘肽化 GAPDH 水平与 AD 进展之间的相关性。作为对照，我们招募了 191 名无 AD 的人，其中包括 111 名健康个体和 37 名患有抑郁症和失眠症的患者，这些人在身心诊所就诊。此外，在神经科诊所招募了 47 名 AD 患者（年龄 40-89 岁）。AD 患者的血液 S-谷胱甘肽化 GAPDH 水平明显（p<0.001）升高（752.7±301.7ng/dL），高于对照组（59.92±122.4ng/dL），与性别和年龄无关。对于 AD 的诊断，标准血液 S-谷胱甘肽化 GAPDH 水平>251.62ng/dL 具有 95.74%的灵敏度和 92.67%的特异性。实际上，年龄在 70-89 岁的个体，即身心诊所的 37 名患者和 42 名健康个体，表现出明显的血液 S-谷胱甘肽化 GAPDH 水平（分别为 230.5±79.3 和 8.05±20.51ng/dL）。这一发现可能表明身心患者的神经退行性 AD 进展，并且表明可以基于血液中 S-谷胱甘肽化 GAPDH 的水平来敏感地评估 AD 进展过程中的神经元凋亡程度。
