| First Author | Tzeng TC | Year | 2018 |
| Journal | Proc Natl Acad Sci U S A | Volume | 115 |
| Issue | 36 | Pages | 9002-9007 |
| PubMed ID | 30127003 | Mgi Jnum | J:265540 |
| Mgi Id | MGI:6197882 | Doi | 10.1073/pnas.1801802115 |
| Citation | Tzeng TC, et al. (2018) Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice. Proc Natl Acad Sci U S A 115(36):9002-9007 |
| abstractText | Alzheimer's disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1DeltaE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1beta or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD. |
