Negative association between nodular stromal fibrosis and large lipid droplets in human choroid plexus epithelial cells

Fibrosis is an age-related change within the human choroid plexus that is likely to affect its function negatively. We systematically analyzed nodular stromal fibrosis present in postmortem tissue from a large repository encompassing the human lifespan. Following manual annotation of sampled images from 81 specimens of choroid plexus from the atrium of the lateral ventricle, a deep learning model was trained to assess stages of fibrosis (dense, hyalinized, and mineralized) occurring in papillae across whole slide images of hematoxylin and eosin-stained sections from 204 cases. The percentage of affected papillae and the relative area of fibrosis at all three stages of severity increased with age. Affected papillae were significantly clustered across the choroid plexus, with areas of high and low fibrotic density. Choroid plexus epithelial cells (CPECs) associated with fibrotic papillae were less likely to contain large lipid droplets than were non-fibrotic papillae, as assessed by another deep learning model. Across papillae within a case, the area of each stage of fibrosis was negatively correlated with the prevalence of CPECs containing large lipid droplets. Finally, individuals displaying more nodular fibrosis had significantly fewer CPECs containing large lipid droplets. Thus, age-related nodular stromal fibrosis may negatively impact lipid storage and homeostasis for the choroid plexus and brain.