- Countries/Regions
- United States of America
- Category
- Research
- Academic Field
- Medicine
- Related goals of SDGs
Information on Niigata University
| Name of the professor/researcher |
Toshikuni Sasaoka |
| Position/Faculty |
Professor, Brain Research Institute |
Information on the Counterpart
| Countries/Regions |
United States of America |
| Faculty/Institution |
University of Massachusetts Medical School |
Detailed Information/Report on Activities
Alzheimer’s disease (AD) is a devastating neurodegenerative disorder leading to profound cognitive decline. Coupled with well-described behavioral manifestations, epileptic seizures are frequently observed in AD patients. Importantly, AD patients have a 2- to 6- fold increased risk of developing seizures compared with age-matched controls. Furthermore, a longitudinal study suggests that ~70% of AD patients will develop seizures during the course of their illness and that seizures adversely affect disease progression. Recent evidence suggests an association between inflammation and epilepsy, although it remains unclear to what degree inflammation causes seizure susceptibility in AD. This research proposal focuses on this critical question.
We previously discovered that amyloid β activates NLRP3 inflammasomes and that AD patients uniformly have evidence of activated inflammasomes in their brains. NLRP3 inflammasomes regulate the expression of IL-1β and IL18, which are pro-inflammatory cytokines. Importantly, we have recently reported that IL18 protects against lethal epilepsy in an AD mouse model by regulating excitatory synaptic function. Furthermore, our preliminary study suggests that IL-1β act as a pro-epileptic cytokine in AD brains. Our results strongly suggest distinct roles for IL-1β and IL18 in AD brains, but our knowledge about the cell types expressing these cytokines during AD pathogenesis is limited. In this proposal, we will test our working hypothesis: IL-1β and IL18 are pro- and anti- pathogenic cytokines in AD, respectively.
