Abdullah Mohammad, Kimura Noriyuki, Akatsu Hiroyasu, Hashizume Yoshio, Ferdous Taslima, Tachita Takuto, Iida Shinsuke, Zou Kun, Matsubara Etsuro, Michikawa Makoto
Department of Biochemistry, Nagoya City University Graduate School of Medical Sciences, Mizuho-cyo, Mizuho-ku, Nagoya, Aichi, Japan.
Department of Neurology, Faculty of Medicine, Oita University, Hazama, Yufu, Oita, Japan.
J Alzheimers Dis. 2019;72(4):1165-1176. doi: 10.3233/JAD-190908.
Currently, best-characterized indicators for Alzheimer's disease (AD) diagnosis are the decreased levels of amyloid-β protein 42 and increased levels of phosphorylated tau in cerebrospinal fluid (CSF). The positron emission tomography (PET) imaging with Pittsburgh compound B (PiB) is also used in AD diagnosis by visualizing amyloid deposition in the brain. These methods are invasive or expensive; therefore, less invasive and easily detectable blood biomarkers are required. Because our previous study showed that flotillin release, a marker of exosomes, was attenuated by Aβ, we designed the present study to determine whether flotillin level could be reduced in CSF and/or serum of patients with AD. In this study, we analyzed flotillin levels in CSF and serum of non-AD controls, patients with AD and mild cognitive impairment (MCI) by western blotting. Flotillin levels in cerebroventricular fluid (CVF) and serum of AD, vascular dementia (VaD), and non-AD autopsy cases were also analyzed. Flotillin levels significantly decreased in the CSF and serum of AD patients compared with those of non-AD controls, respectively. Moreover, in patients with MCI due to AD determined by PiB-PET, CSF and serum flotillin levels significantly decreased compared with those of patients with MCI due to non-AD. Flotillin levels remained unchanged in CVF and serum of autopsy cases diagnosed as VaD. Serum flotillin level is negatively associated with brain amyloid deposition indicated as PiB uptake. These results demonstrate that serum flotillin level can serve as one of the blood markers for estimation of brain amyloid deposition and early diagnosis of AD.
目前，阿尔茨海默病（AD）诊断中最具特征性的指标是脑脊液（CSF）中β淀粉样蛋白42水平降低和磷酸化tau蛋白水平升高。使用匹兹堡化合物B（PiB）的正电子发射断层扫描（PET）成像也可通过观察大脑中的淀粉样蛋白沉积用于AD诊断。这些方法具有侵入性或成本高昂；因此，需要侵入性较小且易于检测的血液生物标志物。由于我们之前的研究表明，外泌体标志物 flotillin释放会被Aβ减弱，我们设计了本研究以确定AD患者的脑脊液和/或血清中flotillin水平是否会降低。在本研究中，我们通过蛋白质印迹法分析了非AD对照、AD患者和轻度认知障碍（MCI）患者脑脊液和血清中的flotillin水平。还分析了AD、血管性痴呆（VaD）和非AD尸检病例的脑室液（CVF）和血清中的flotillin水平。与非AD对照相比，AD患者脑脊液和血清中的flotillin水平分别显著降低。此外，在由PiB-PET确定为AD所致MCI的患者中，脑脊液和血清flotillin水平与非AD所致MCI患者相比显著降低。在诊断为VaD的尸检病例的CVF和血清中，flotillin水平保持不变。血清flotillin水平与以PiB摄取表示的脑淀粉样蛋白沉积呈负相关。这些结果表明，血清flotillin水平可作为评估脑淀粉样蛋白沉积和AD早期诊断的血液标志物之一。
