Li He, Ye Tianyuan, Liu Xingyang, Guo Rui, Yang Xiuzhao, Li Yangyi, Qi Dongmei, Wei Yihua, Zhu Yifan, Wen Lei, Cheng Xiaorui
Innovative Institute of Chinese Medicine and Pharmacy, Shandong University of Traditional Chinese Medicine, Jinan, 250355, China.
Xiamen Key Laboratory for TCM Dampness Disease, Neurology & Immunology Research, Department of Traditional Chinese Medicine, Xiang'an Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361102, China.
J Pharm Anal. 2023 Jul;13(7):788-805. doi: 10.1016/j.jpha.2023.05.008. Epub 2023 May 15.
Based on single-cell sequencing of the hippocampi of 5× familiar Alzheimer's disease (5× FAD) and wild type mice at 2-, 12-, and 24-month of age, we found an increased percentage of microglia in aging and Alzheimer's disease (AD) mice. Blood brain barrier injury may also have contributed to this increase. Immune regulation by microglia plays a major role in the progression of aging and AD, according to the functions of 41 intersecting differentially expressed genes in microglia. Signaling crosstalk between C-C motif chemokine ligand (CCL) and major histocompatibility complex-1 bridges intercellular communication in the hippocampus during aging and AD. The amyloid precursor protein (APP) and colony stimulating factor (CSF) signals drive 5× FAD to deviate from aging track to AD occurrence among intercellular communication in hippocampus. Microglia are involved in the progression of aging and AD can be divided into 10 functional types. The strength of the interaction among microglial subtypes weakened with aging, and the CCL and CSF signaling pathways were the fundamental bridge of communication among microglial subtypes.
基于对5倍体家族性阿尔茨海默病（5×FAD）和野生型小鼠在2个月、12个月和24个月龄时海马体的单细胞测序，我们发现衰老和阿尔茨海默病（AD）小鼠中微胶质细胞的百分比增加。血脑屏障损伤可能也促成了这种增加。根据微胶质细胞中41个交叉差异表达基因的功能，微胶质细胞的免疫调节在衰老和AD的进展中起主要作用。在衰老和AD过程中，C-C基序趋化因子配体（CCL）和主要组织相容性复合体-1之间的信号串扰在海马体中建立了细胞间通讯。淀粉样前体蛋白（APP）和集落刺激因子（CSF）信号在海马体的细胞间通讯中驱动5×FAD从衰老轨迹偏离至AD发生。微胶质细胞参与衰老和AD进展可分为10种功能类型。随着衰老，微胶质细胞亚型之间相互作用的强度减弱，CCL和CSF信号通路是微胶质细胞亚型之间通讯的基本桥梁。
