TY - JOUR T1 - Timapiprant, a prostaglandin D2 receptor antagonist, ameliorates pathology in a rat Alzheimer’s model JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202201555 VL - 5 IS - 12 SP - e202201555 AU - Charles H Wallace AU - Giovanni Oliveros AU - Peter A Serrano AU - Patricia Rockwell AU - Lei Xie AU - Maria Figueiredo-Pereira Y1 - 2022/12/01 UR - https://www.life-science-alliance.org/content/5/12/e202201555.abstract N2 - We investigated the relevance of the prostaglandin D2 pathway in Alzheimer’s disease, because prostaglandin D2 is a major prostaglandin in the brain. Thus, its contribution to Alzheimer’s disease merits attention, given the known impact of the prostaglandin E2 pathway in Alzheimer’s disease. We used the TgF344-AD transgenic rat model because it exhibits age-dependent and progressive Alzheimer’s disease pathology. Prostaglandin D2 levels in hippocampi of TgF344-AD and wild-type littermates were significantly higher than prostaglandin E2. Prostaglandin D2 signals through DP1 and DP2 receptors. Microglial DP1 receptors were more abundant and neuronal DP2 receptors were fewer in TgF344-AD than in wild-type rats. Expression of the major brain prostaglandin D2 synthase (lipocalin-type PGDS) was the highest among 33 genes involved in the prostaglandin D2 and prostaglandin E2 pathways. We treated a subset of rats (wild-type and TgF344-AD males) with timapiprant, a potent highly selective DP2 antagonist in development for allergic inflammation treatment. Timapiprant significantly mitigated Alzheimer’s disease pathology and cognitive deficits in TgF344-AD males. Thus, selective DP2 antagonists have potential as therapeutics to treat Alzheimer’s disease. ER -