Research Topic 1: Investigating the Role of Choroid Plexus in Alzheimer's Disease Pathology

The detection of Alzheimer's disease in its early stages is a significant challenge in healthcare, and understanding the pathological pathways involved in its development and progression is crucial. To address this issue, we aim to investigate the role of the choroid plexus in both healthy and diseased states using interdisciplinary and integrative approaches. Our research involves transcriptomic and translational profiling, as well as Artificial Intelligence (AI), to uncover molecular events and alterations in the choroid plexus during Alzheimer's disease development.

Additionally, Dr Zamani is part of a consortium aimed at developing animal models of Alzheimer's disease. This consortium includes researchers from Charles University in Prague and Pilsen, as well as the Czech National Institute of Mental Health. This has provided us with the opportunity to employ various animal models to study the complex role of the choroid plexus in Alzheimer's disease. We also collaborate with experts from different fields, both within and outside the Czech Republic, to investigate this disease from multiple perspectives and discover new therapeutic strategies for the prevention and treatment of Alzheimer's disease, ultimately improving the quality of life for affected individuals.

Research Topic 2: Studying the involvement of the choroid plexus in chemotherapy-induced neuropathy

Chemotherapy often leads to long-lasting and irreversible neuropathic pain. One potential pathway for the transfer of peripheral immune signals and cells to the central nervous system is through the choroid plexus. Our previous research has shown that paclitaxel, a widely used chemotherapy agent, can induce significant changes in the inflammatory profile of the choroid plexus. However, it is unclear whether these changes impact the integrity of the blood-cerebrospinal fluid barrier, which, if compromised, could lead to immune cell infiltration into the brain and activation of the pain pathway.

Therefore, we aim to investigate the underlying mechanisms of the spread of peripheral inflammation into the central nervous system via the choroid plexus. Our initial findings demonstrate that male rats subjected to chemotherapy display an increased number of macrophages in the choroid plexus. Further investigation is necessary to determine whether these macrophages are recruited from the peripheral system due to a compromised barrier and whether their presence may affect its functional structure. Additionally, we aim to investigate potential differences in this response between male and female rats.

To accomplish this, we use both animal and in vitro models and employ an integrative approach that includes translational profiling of the choroid plexus. Additionally, we collaborate with data scientists to develop prediction models that could help identify patients at risk for developing neuropathic pain during chemotherapy treatment.