The role of signaling crosstalk of microglia in hippocampus on progression of ageing and Alzheimer's disease

• Published in: Journal of pharmaceutical analysis 2023-07, Vol.13 (7), p.788-805
• Main Authors: Li, He, Ye, Tianyuan, Liu, Xingyang, Guo, Rui, Yang, Xiuzhao, Li, Yangyi, Qi, Dongmei, Wei, Yihua, Zhu, Yifan, Wen, Lei, Cheng, Xiaorui
• Format: Article
• Language: English
• Subjects: Aging; Alzheimer's disease; Amyloid precursor protein; Animal cognition; Behavior; Biotechnology; Blood-brain barrier; Brain injury; Brain research; Cerebrospinal fluid; Chemokines; Chinese medicine; Cognitive ability; Colony-stimulating factor; Communication; Dementia; Genomics; Hippocampus; Immunoregulation; Ligands; Major histocompatibility complex; Medical research; Microglia; Neurodegenerative diseases; Proteins; Software
• ISSN: 2095-1779; 2214-0883
• DOI: 10.1016/jjpha.2023.05.008

Based on single-cell sequencing of the hippocampi of 5x familiar Alzheimer's disease (5x 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-l bridges intercellular communication in the hippocampus during aging and AD. The amyloid precursor protein (APP) and colony stimulating factor (CSF) signals drive 5x 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.