This project study the involvement of estrogen receptors, in particular ERb, in the molecular mechanisms behind estrogenic neuroprotection in AD. This will be performed primarily in two models of AD; AppNLGF mouse model of early-onset AD, and AppNLF mouse model of late-onset AD (App knockin [App-KI]). This includes single cell RNA-sequencing (scRNA-seq) anayses in male and female mouse hippocampi. The data will be validated against human AD brain samples or human transcriptomic data. If possible, it will be followed up with regards to hormonal therapy (HT) use and possible confounding/interacting chronic disease history will be explored. We will also study the vascular profile of the App-KI models using scRNA-seq. Thus, the overall aim of this project is to address the molecular underpinnings of estrogenic neuroprotection in models of AD and put it in relation to human AD and the sex differences observed in this disease.