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Investigate the Role of Choroid Plexus in Alzheimer’s Disease

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JEŘÁBKOVÁ Karolína ORVISKÁ Petra ZARERAVASAN Ahad DIANAT Malahatosadat JOUKAL Andrea EMAMIAREF Parisa BRÁZDA Václav ZAMANI Alemeh

Rok publikování 2024
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Popis Alzheimer's disease is a progressive neurodegenerative disorder characterized by the gradual worsening of dementia over several years, eventually becoming completely debilitating in its later stages. The three hallmark features of AD are amyloid-beta (Aß) aggregation, tau hyperphosphorylation, and neuroinflammation. However, the precise sequential relationship among these phenomena remains unclear. The Choroid Plexus, which forms the blood-cerebrospinal fluid barrier, plays a crucial role in the clearance of Aß from the brain. In Alzheimer's disease, insufficient Aß clearance and increased inflammatory changes in the choroid plexus and cerebrospinal fluid are observed. This study investigates the underlying mechanism by which the choroid plexus is altered during Alzheimer’s disease. We used an in vitro model of Alzheimer’s disease in Z310 cells developed in our lab. The choroidal epithelial cells, Z310 cells, were incubated with Aß peptide for various time points, and molecular techniques were used to investigate the Z310 cell alterations. We showed the molecular structure alteration of Z310 cells as early as 1 hour after the Aß treatment. We observed a significant increase in molecular alteration with time. Alzheimer’s disease-associated molecules, such as amyloid precursor protein (APP) and inflammatory mediators, were found to be among the molecules that exhibited alterations. Furthermore, proteins responsible for the barrier properties were demonstrated to be influenced by treatment with Aß. Our results provide valuable insights into the importance of understanding the role of the choroid plexus in the early stages of the disease. This includes its contribution to disease progression as well as its protective functions.
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