Back

sKL/mKL Transcript Ratio and Protein Localization Define a Species- and Region-Specific Klotho Signature in the CNS and AD Progression

Blanch, R.; Esandi, J.; Guerrero-Yagüe, R.; Del Rey, J.; Roig-Soriano, J.; Lleo, A.; Carro, E.; Mestre-Frances, N.; Devau, G.; Ferrer, I.; Meseguer, A.; Lanciego, J. L.; Almolda, B.; Bosch, A.; Chillon, M.

2025-05-17 neuroscience
10.1101/2025.05.13.653838 bioRxiv
Show abstract

-Klotho is a multifunctional protein widely recognized for its anti-aging and neuroprotective properties. This study investigates the expression and localization of the secreted Klotho (s-KL) isoform in the human brain and its potential role in Alzheimers disease. Using RT-qPCR, we observed that the s-KL transcript predominates over the membrane-bound KL (m-KL) in multiple brain regions, a pattern consistent in macaques and lemurs. Immunohistochemistry and immunoprecipitation assays confirmed the presence of the s-KL protein in human and mouse brain parenchyma, revealing species-specific cellular localization. In human cerebrospinal fluid (CSF), s-KL constitutes [~]28% of total KL, with levels significantly reduced in mild dementia-AD patients. These findings underscore s-KLs potential neuroprotective role and highlight its differential regulation and expression during AD progression.

Matching journals

The top 10 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.