Uehara Yoshinari, Yamada Tatsuo, Baba Yasuhiko, Miura Shin-ichiro, Abe Satomi, Kitajima Ken, Higuchi Masa-aki, Iwamoto Takahiro, Saku Keijiro
Department of Pharmacology, Fukuoka University Faculty of Medicine, 7-45-1 Nanakuma, Jonan-ku, Fukuoka, Japan.
Brain Res. 2008 Jun 27;1217:239-46. doi: 10.1016/j.brainres.2008.04.048. Epub 2008 Apr 27.
Apolipoprotein E epsilon4 is an independent risk factor for Alzheimer's disease (AD) and is the main constituent of high-density lipoprotein (HDL) as a source of cholesterol in the brain. ATP-binding cassette transporter G4 (ABCG4) is one of the membrane cholesterol transporter which is implicated in HDL-mediated cholesterol efflux, but its precise localization and function in the brain has been unclear. In AD brain, ABCG4 protein was highly expressed in microglial cell that was closely located to senile plaques, whereas in non-neurological cases positive cells were not seen in cortical and nigral tissues. As well as the ABCG4 protein, ABCG4 mRNA signal was detected in microglial cell closely located to senile plaque of AD brain by in situ hybridization histochemistry. These results suggest that upregulated ABCG4 in microglia may accelerate the lipidation of apoE and HDL in the AD brain. This is the first report to show that ABCG4 is highly expressed in microglia on AD brain.
载脂蛋白Eε4是阿尔茨海默病（AD）的独立危险因素，并且作为大脑中胆固醇的来源，它是高密度脂蛋白（HDL）的主要成分。ATP结合盒转运蛋白G4（ABCG4）是参与HDL介导的胆固醇流出的膜胆固醇转运蛋白之一，但其在大脑中的精确定位和功能尚不清楚。在AD大脑中，ABCG4蛋白在紧邻老年斑的小胶质细胞中高表达，而在非神经病例的皮质和黑质组织中未见阳性细胞。通过原位杂交组织化学，在紧邻AD大脑老年斑的小胶质细胞中检测到ABCG4 mRNA信号，与ABCG4蛋白情况相同。这些结果表明，小胶质细胞中上调的ABCG4可能加速AD大脑中载脂蛋白E和HDL的脂化。这是首份表明ABCG4在AD大脑的小胶质细胞中高表达的报告。
