# Steroid signaling in the choroid plexus of the aging brain

> **NIH NIH R03** · UNIVERSITY OF CALIFORNIA BERKELEY · 2021 · $273,807

## Abstract

Recent studies have found that women are bearing a disproportionate amount of the
Alzheimer’s disease
this disease
it produces less progesterone and estrogens and there is a
correlation between early onset of menopause (and hence a decline in sex steroid levels) with increased
Alzheimer’s disease susceptibility. Steroid hormones regulate physiology of many tissues, among which is the
choroid plexus- an epithelial tissue responsible for secretion of cerebrospinal fluid (CSF), the fluid that protects
the brain, provides it with nutrients and hormones, and removes waste products. With aging, the choroid
plexus fails to maintain adequate CSF production and turnover and this may contribute to the onset of
cognitive decline and development of the Alzheimer’s disease
the molecular mechanism of its action remains
burden: at the age of 65, women have a 1 in 5 chance of developing , compared to a 1 in 11
chance for men. As the female body ages,
. Steroid hormone progesterone is known to
regulate fluid homeostasis in the choroid plexus, however,
elusive.
We recently discovered that while choroid plexus does not express any canonical nuclear-localized
progesterone receptors, it does highly express the unconventional membrane progesterone receptor α/β
hydrolase domain–containing protein 2 (ABHD2). Global knockout of
Abhd2 produces mice with
smaller brain
ventricles and narrower
choroid plexus
capillaries. Our preliminary data indicate the steroid signaling in the
choroid plexus , and since steroid levels decline with age, turnover of CSF
production may be altered by a narrower choroid plexus capillary network due to decreased steroid content.
we seek to study (1) the physiological role of ABHD2 and its downstream effectors in the choroid plexus
of the aging brain by generating conditional knockouts of Abhd2 and other targeted genes specifically in the
choroid plexus; and (2) to explore the mechanism between CSF turnover with age and the role steroid
hormones play in it. Our team has matching expertise in acute tissue-specific gene knockdown in the aging
mouse brain and biophysical characterization of the choroid plexus function. The outcome of this research will
help to establish physiological role of ABHD2 in the choroid plexus and its alteration during aging and
Alzheimer’s disease. Additionally, this work will reveal novel
could be linked to CSF turnover
Here
molecular pathways that may explain gender-
differences in steroid regulation of CSF production and why Alzheimer’s disease affects women at a higher
rate. Finally,
data obtained from this project will form the basis for a joint R01 grant application, which will allow
us to expand our teams’ research on steroid regulation of the brain function and its role in Alzheimer’s disease.

## Key facts

- **NIH application ID:** 10117618
- **Project number:** 1R03AG070755-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA BERKELEY
- **Principal Investigator:** Jennifer L Garrison
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $273,807
- **Award type:** 1
- **Project period:** 2021-03-15 → 2023-01-01

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10117618

## Citation

> US National Institutes of Health, RePORTER application 10117618, Steroid signaling in the choroid plexus of the aging brain (1R03AG070755-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10117618. Licensed CC0.

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