| First Author | Zhang C | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 1144 |
| PubMed ID | 29348604 | Mgi Jnum | J:260232 |
| Mgi Id | MGI:6148472 | Doi | 10.1038/s41598-018-19641-2 |
| Citation | Zhang C, et al. (2018) Cromolyn Reduces Levels of the Alzheimer's Disease-Associated Amyloid beta-Protein by Promoting Microglial Phagocytosis. Sci Rep 8(1):1144 |
| abstractText | Amyloid-beta protein (Abeta) deposition is a pathological hallmark of Alzheimer''s disease (AD). Abeta deposition triggers both pro-neuroinflammatory microglial activation and neurofibrillary tangle formation. Cromolyn sodium is an asthma therapeutic agent previously shown to reduce Abeta levels in transgenic AD mouse brains after one-week of treatment. Here, we further explored these effects as well as the mechanism of action of cromolyn, alone, and in combination with ibuprofen in APP(Swedish)-expressing Tg2576 mice. Mice were treated for 3 months starting at 5 months of age, when the earliest stages of beta-amyloid deposition begin. Cromolyn, alone, or in combination with ibuprofen, almost completely abolished longer insoluble Abeta species, i.e. Abeta40 and Abeta42, but increased insoluble Abeta38 levels. In addition to its anti-aggregation effects on Abeta, cromolyn, alone, or plus ibuprofen, but not ibuprofen alone, increased microglial recruitment to, and phagocytosis of beta-amyloid deposits in AD mice. Cromolyn also promoted Abeta42 uptake in microglial cell-based assays. Collectively, our data reveal robust effects of cromolyn, alone, or in combination with ibuprofen, in reducing aggregation-prone Abeta levels and inducing a neuroprotective microglial activation state favoring Abeta phagocytosis versus a pro-neuroinflammatory state. These findings support the use of cromolyn, alone, or with ibuprofen, as a potential AD therapeutic. |
