| First Author | Dhawan G | Year | 2012 |
| Journal | Neurobiol Aging | Volume | 33 |
| Issue | 10 | Pages | 2247-61 |
| PubMed ID | 22133278 | Mgi Jnum | J:191178 |
| Mgi Id | MGI:5461138 | Doi | 10.1016/j.neurobiolaging.2011.10.027 |
| Citation | Dhawan G, et al. (2012) Amyloid-beta oligomers stimulate microglia through a tyrosine kinase dependent mechanism. Neurobiol Aging 33(10):2247-61 |
| abstractText | Alzheimer''s disease (AD) has been well characterized by the presence of reactive microglia, often associated with beta-amyloid (Abeta) plaque deposition. The oligomeric form of Abeta peptide (Abeta(o)) has neurotoxic effects in the presence of microglia and is suggested to potentiate proinflammatory changes in microglia in AD. Primary murine microglia cultures stimulated with Abeta(o) displayed increased protein phosphotyrosine and secreted tumor necrosis factor (TNF)-alpha levels which were attenuated by the Src/Abl inhibitor, dasatinib. Intracerebroventricular infusions of Abeta(o) into C57BL6/J mice stimulated increased microgliosis and protein phosphotyrosine levels that were also attenuated by dasatinib administration. The rodent findings were validated in human AD brains versus age-matched controls demonstrating reactive microglial association with Abeta(o) deposits and increased microglial protein phosphotyrosine and phospho-Src levels. These data suggest a role for Abeta(o) in microglial activation through a tyrosine kinase-dependant pathway both in rodent models and human disease. Use of a selective nonreceptor tyrosine kinase inhibitor such as dasatinib to attenuate microglial-dependent proinflammatory changes may prove to be an important step toward developing anti-inflammatory treatments for AD. |
