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[Preprint]. 2026 May 26:2026.05.21.725559. [Version 1] doi: 10.64898/2026.05.21.725559

Inducible lipid storage and steatosis in the human choroid plexus associated with age and adiposity

N Victoria Espericueta, Michael J Neel, Yao Wang, Todd J Soo, Parastou Porahang, Frances A Goyokpin, Ryan S Salehi, Sara Khan, Jasmine Lee, Nicolas B Maramica, Guillermo Flores, Aditi Kulkarni, Sahil S Plaha, Sam Ghahremani, William Huang, Quinton Smith, Peter Chang, Brett A Johnson, Edwin S Monuki
PMCID: PMC13232116  PMID: 42244608

ABSTRACT

Cells that store lipids for other cells or organs can contain “giant” or large lipid droplets (LLDs) greater than 2 µm in diameter. In this study, human postmortem choroid plexus was evaluated for lipid droplets. Staining with hematoxylin and eosin (H&E), the lipophilic dye Oil red O, and anti-adipophilin antibodies established the presence of LLDs exceeding 10 µm in diameter in choroid plexus epithelial cells (CPECs). Manual annotation of H&E stains from 105 cases revealed a significant association between age and the percentage of CPECs containing LLDs (reaching up to 69%) and involving LLDs in our largest annotated category (>5 µm in diameter). The LLD association with age was replicated and extended to a total of 245 cases using a trained convolutional neural network, which further showed significant associations with body mass index at time of death (increasing with BMI), sex (higher in females >65 years old), and a near-significant association with Alzheimer’s Disease (lower in AD). Like HepG2 and derived hepatocytes, excess fatty acids in culture media readily induced LLDs and steatosis in human embryonic stem cell-derived CPECs. Akin to hepatocytes for the human body, we propose that CPECs store lipids for the human brain and become steatotic in the setting of excess adiposity.

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