| First Author | Smit T | Year | 2022 |
| Journal | Brain Behav Immun | Volume | 100 |
| Pages | 219-230 | PubMed ID | 34896594 |
| Mgi Jnum | J:348505 | Mgi Id | MGI:6865360 |
| Doi | 10.1016/j.bbi.2021.12.001 | Citation | Smit T, et al. (2022) Transcriptomic and functional analysis of Abeta1-42 oligomer-stimulated human monocyte-derived microglia-like cells. Brain Behav Immun 100:219-230 |
| abstractText | Dysregulation of microglial function contributes to Alzheimer's disease (AD) pathogenesis. Several genetic and transcriptome studies have revealed microglia specific genetic risk factors, and changes in microglia expression profiles in AD pathogenesis, viz. the human-Alzheimer's microglia/myeloid (HAM) profile in AD patients and the disease-associated microglia profile (DAM) in AD mouse models. The transcriptional changes involve genes in immune and inflammatory pathways, and in pathways associated with Abeta clearance. Abeta oligomers have been suggested to be the initial trigger of microglia activation in AD. To study the direct response to Abeta oligomers exposure, we assessed changes in gene expression in an in vitro model for microglia, the human monocyte-derived microglial-like (MDMi) cells. We confirmed the initiation of an inflammatory profile following LPS stimulation, based on increased expression of IL1B, IL6, and TNFalpha. In contrast, the Abeta1-42 oligomers did not induce an inflammatory profile or a classical HAM profile. Interestingly, we observed a specific increase in the expression of metallothioneins in the Abeta1-42 oligomer treated MDMi cells. Metallothioneins are involved in metal ion regulation, protection against reactive oxygen species, and have anti-inflammatory properties. In conclusion, our data suggests that exposure to Abeta1-42 oligomers may initially trigger a protective response in vitro. |
