sKL/mKL Transcript Ratio and Protein Localization Define a Species- and Region-Specific Klotho Signature in the CNS and AD Progression
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 Alzheimer\'s 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-KL\'s potential neuroprotective role and highlight its differential regulation and expression during AD progression.
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Research summary
The study claims that the secreted Klotho isoform (s-KL) is differentially expressed in the brain and cerebrospinal fluid of Alzheimer's disease patients, suggesting a potential neuroprotective role. The research is relevant as it explores the role of Klotho in neuroprotection and its implications for Alzheimer's disease, which is a significant age-related condition.
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