Hoshi Kyoka, Kanno Mayumi, Abe Mitsunari, Murakami Takenobu, Ugawa Yoshikazu, Goto Aya, Honda Takashi, Saito Takashi, Saido Takaomi C, Yamaguchi Yoshiki, Miyajima Masakazu, Furukawa Katsutoshi, Arai Hiroyuki, Hashimoto Yasuhiro
Department of Biochemistry, Fukushima Medical University, Fukushima 960-1295, Japan.
Department of Forensic Medicine, Fukushima Medical University, Fukushima 960-1295, Japan.
Metabolites. 2022 Apr 15;12(4):355. doi: 10.3390/metabo12040355.
The cerebrospinal fluid (CSF) plays an important role in homeostasis of the brain. We previously demonstrated that major CSF proteins such as lipocalin-type prostaglandin D2 synthase (L-PGDS) and transferrin (Tf) that are biosynthesized in the brain could be biomarkers of altered CSF production. Here we report that the levels of these brain-derived CSF proteins correlated well with each other across various neurodegenerative diseases, including Alzheimer's disease (AD). In addition, protein levels tended to be increased in the CSF samples of AD patients compared with the other diseases. Patients at memory clinics were classified into three categories, consisting of AD ( = 61), mild cognitive impairment (MCI) ( = 42), and cognitively normal (CN) ( = 23), with MMSE scores of 20.4 ± 4.2, 26.9 ± 1.7, and 29.0 ± 1.6, respectively. In each category, CSF protein levels were highly correlated with each other. In CN subjects, increased CSF protein levels correlated well with those of AD markers, including amyloid-β and tau protein, whereas in MCI and AD subjects, correlations declined with AD markers except p-tau. Future follow-up on each clinical subject may provide a clue that the CSF proteins would be AD-related biomarkers.
脑脊液（CSF）在大脑的内环境稳定中起着重要作用。我们之前证明，大脑中生物合成的主要脑脊液蛋白，如脂钙蛋白型前列腺素D2合酶（L-PGDS）和转铁蛋白（Tf），可能是脑脊液生成改变的生物标志物。在此我们报告，在包括阿尔茨海默病（AD）在内的各种神经退行性疾病中，这些源自大脑的脑脊液蛋白水平彼此之间具有良好的相关性。此外，与其他疾病相比，AD患者脑脊液样本中的蛋白水平往往会升高。记忆门诊的患者被分为三类，包括AD患者（n = 61）、轻度认知障碍（MCI）患者（n = 42）和认知正常（CN）者（n = 23），简易精神状态检查表（MMSE）评分分别为20.4±4.2、26.9±1.7和29.0±1.6。在每一类中，脑脊液蛋白水平彼此之间高度相关。在CN受试者中，脑脊液蛋白水平升高与AD标志物（包括淀粉样β蛋白和tau蛋白）的水平具有良好的相关性，而在MCI和AD受试者中，除了磷酸化tau蛋白外，与AD标志物的相关性下降。对每个临床受试者的未来随访可能会提供线索，表明脑脊液蛋白将是与AD相关的生物标志物。
