促炎细胞因子
神经病理学
表型
神经可塑性
微生物群
免疫系统
生物
表型可塑性
骨髓
免疫学
细胞生物学
神经科学
医学
炎症
病理
生物信息学
遗传学
基因
疾病
作者
Ruth Iban-Arias,Eun‐Jeong Yang,Elizabeth Griggs,Anayda Portela,Aya Osman,Kyle J. Trageser,Mahadi Shahed,Giulio Maria Pasinetti
标识
DOI:10.1016/j.bbi.2024.03.012
摘要
Immune system dysfunction is increasingly recognized as a significant feature that contributes to Alzheimer’s disease (AD) pathogenesis, reflected by alterations in central and peripheral responses leading to detrimental mechanisms that can contribute to the worsening of the disease. The damaging alterations in the peripheral immune system may disrupt the peripheral-central immune crosstalk, implicating the gut microbiota in this complex interaction. The central hypothesis posits that the immune signature inherently harbored in bone marrow (BM) cells can be transferred through allogeneic transplantation, influencing the recipient’s immune system and modulating peripheral, gut, and brain immune responses. Employing a genetically modified mouse model to develop AD-type pathology we found that recipient wild-type (WT) mice engrafted with AD-derived BM, recapitulated the peripheral immune inflammatory donor phenotype, associated with a significant acceleration of cognitive deterioration in the absence of any overt change in AD-type amyloid neuropathology. Moreover, transcriptomic and phylogenetic 16S microbiome analysis evidence on these animals revealed a significantly impaired expression of genes associated with synaptic plasticity and neurotransmission in the brain and reduced bacteria diversity, respectively, compared to mice engrafted with WT BM. This investigation sheds light on the pivotal role of the peripheral immune system in the brain-gut-periphery axis and its profound potential to shape the trajectory of AD. In summary, this study advances our understanding of the complex interplay among the peripheral immune system, brain functionality, and the gut microbiome, which collectively influence AD onset and progression.
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