# Regulation of choroid plexus epithelial function by klotho

> **NIH NIH R15** · CREIGHTON UNIVERSITY · 2021 · $436,500

## Abstract

PROJECT SUMMARY
Age-related changes to protein and thus cellular function occur across the brain. Increased understanding of
when age-related events become pathological is required both to support healthy brain aging and to develop
early and efficacious neurodegenerative disease therapeutics. Among the cells of the brain to experience age-
related impairment to structure and function, the choroid plexus epithelial cells stand out as a tissue with
untapped potential to support the entire brain parenchyma. Choroid plexus epithelial cells express high levels
of Klotho protein. Increasing expression of Klotho enhances but decreasing expression impairs neuronal
memory function across species and in models of neurodegenerative disease. Recent work determined that a
common human polymorphic variant of Klotho that increases protein is protective against Alzheimer’s disease
development and pathology. While Klotho action in and upon cells of the brain parenchyma indicates its effects
are brain-wide, little is known about the primary source of brain Klotho, the choroid plexus epithelial cells. Our
pilot data indicate that cell-type specific klotho-deficiency impacts longevity, memory, and choroid plexus cell
structure and function. These data suggest that Klotho may effects cells throughout the brain because it is
critical to choroid plexus epithelial cell activities. Choroid plexus epithelial cells provide physical, nutrient, and
signal transduction support to the entire brain. They also function as a physical protective barrier and
communication center between body and brain. The long-term goal of the proposed research is to understand
the health-related functional consequences of age-related klotho-deficiency from choroid plexus epithelial cells.
We will use mouse models to interrogate the central hypothesis that Klotho-deficiency impairs brain
parenchyma by disrupting the function of the choroid plexus epithelial cells. In specific aim one, we will use
mouse models to determine the role of choroid plexus-specific Klotho expression on memory across lifespan.
Using animal models and cellular and molecular techniques, aim two will determine whether choroid plexus
epithelial cell structure or function are altered by Klotho-deficiency. The significance of the proposal lies in
contributions to understanding the basic biology of Klotho as a protein critical for the normal choroid plexus
epithelial cell functions required to sustain and support healthy brain parenchyma across lifespan. We are
uniquely situated to expose undergraduate students interested in research and medically focused careers
discovery neuroscience research using animal models. The proposal is innovative in its use of novel animal
models to allow targeted manipulation of Klotho expression and, in studying the choroid plexus epithelia,
studies a tissue-type with unrealized potential to support brain health across lifespan.

## Key facts

- **NIH application ID:** 10291166
- **Project number:** 1R15AG073947-01
- **Recipient organization:** CREIGHTON UNIVERSITY
- **Principal Investigator:** Gwendalyn DiAnn King
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $436,500
- **Award type:** 1
- **Project period:** 2021-08-15 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10291166

## Citation

> US National Institutes of Health, RePORTER application 10291166, Regulation of choroid plexus epithelial function by klotho (1R15AG073947-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10291166. Licensed CC0.

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