Department of Neuropathology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Brain Pathol. 2018 Jan;28(1):58-71. doi: 10.1111/bpa.12475. Epub 2017 Feb 8.
Adipocyte enhancer binding protein 1 (AEBP1) activates inflammatory responses via the NF-κB pathway in macrophages and regulates adipogenesis in preadipocytes. Up-regulation of AEBP1 in the hippocampi of patients with Alzheimer's disease (AD) has been revealed by microarray analyses of autopsied brains from the Japanese general population (the Hisayama study). In this study, we compared the expression patterns of AEBP1 in normal and AD brains, including in the hippocampus, using immunohistochemistry. The subjects were 24 AD cases and 52 non-AD cases. Brain specimens were immunostained with antibodies against AEBP1, tau protein, amyloid β protein, NF-κB, GFAP and Iba-1. In normal brains, AEBP1 immunoreactivity mainly localized to the perikarya of hippocampal pyramidal neurons, and its expression was elevated in the pyramidal neurons and some astrocytes in AD hippocampi. Although AEBP1 immunoreactivity was almost absent in neurons containing neurofibrillary tangles, AEBP1 was highly expressed in neurons with pretangles and in the tau-immunopositive, dystrophic neurites of senile plaques. Nuclear localization of NF-κB was also observed in certain AEBP1-positive neurons in AD cases. Comparison of AD and non-AD cases suggested a positive correlation between the expression level of AEBP1 and the degree of amyloid β pathology. These findings imply that AEBP1 protein has a role in the progression of AD pathology.
脂肪细胞增强结合蛋白 1(AEBP1)通过 NF-κB 通路在巨噬细胞中激活炎症反应,并在前脂肪细胞中调节脂肪生成。通过对日本普通人群(HISAYAMA 研究)尸检大脑的基因表达谱微阵列分析,发现阿尔茨海默病(AD)患者的海马体中 AEBP1 上调。在这项研究中,我们通过免疫组织化学比较了正常和 AD 大脑中 AEBP1 的表达模式,包括海马体。研究对象为 24 例 AD 病例和 52 例非 AD 病例。脑标本用针对 AEBP1、tau 蛋白、淀粉样β蛋白、NF-κB、GFAP 和 Iba-1 的抗体进行免疫染色。在正常大脑中,AEBP1 免疫反应性主要定位于海马锥体神经元的胞体,在 AD 海马体的锥体神经元和一些星形胶质细胞中其表达上调。虽然含有神经纤维缠结的神经元中几乎没有 AEBP1 免疫反应性,但 AEBP1 在 pretangles 神经元和老年斑中 tau 免疫阳性的、退行性神经突中高度表达。NF-κB 的核定位也在 AD 病例中某些 AEBP1 阳性神经元中观察到。AD 和非 AD 病例的比较表明,AEBP1 表达水平与淀粉样β病理学程度呈正相关。这些发现表明 AEBP1 蛋白在 AD 病理学进展中具有作用。