| First Author | Lim JE | Year | 2011 |
| Journal | Am J Pathol | Volume | 179 |
| Issue | 3 | Pages | 1095-103 |
| PubMed ID | 21763676 | Mgi Jnum | J:176316 |
| Mgi Id | MGI:5290035 | Doi | 10.1016/j.ajpath.2011.05.045 |
| Citation | Lim JE, et al. (2011) MyD88 deficiency ameliorates beta-amyloidosis in an animal model of Alzheimer's disease. Am J Pathol 179(3):1095-103 |
| abstractText | The accumulation of beta-amyloid protein (Abeta) in the brain is thought to be a primary etiologic event in Alzheimer's disease (AD). Fibrillar Abeta plaques, a hallmark of AD abnormality, are closely associated with activated microglia. Activated microglia have contradictory roles in the pathogenesis of AD, being either neuroprotective (by clearing harmful Abeta and repairing damaged tissues) or neurotoxic (by producing proinflammatory cytokines and reactive oxygen species). Abeta aggregates can activate microglia by interacting with multiple toll-like receptors (TLRs), the pattern-recognition receptors of the innate immune system. Because the adapter protein MyD88 is essential for the downstream signaling of all TLRs, except TLR3, we investigated the effects of MyD88 deficiency (MyD88(-/-)) on Abeta accumulation and microglial activation in an AD mouse model. MyD88 deficiency decreased Abeta load and microglial activation in the brain. The decrease in Abeta load in an MyD88(-/-) AD mouse model was associated with increased and decreased protein expression of apolipoprotein E (apoE) and CX3CR1, respectively, compared with that in an MyD88 wild-type AD mouse model. These results suggest that MyD88 deficiency may reduce Abeta load by enhancing the phagocytic capability of microglia through fractalkine (the ligand of CX3CR1) signaling and by promoting apoE-mediated clearance of Abeta from the brain. These findings also suggest that chronic inflammatory responses induced by Abeta accumulation via the MyD88-dependent signaling pathway exacerbate beta-amyloidosis in AD. |
