Award
NIH Reporter #1R21AG104396-01
An Overlooked Steroid Hormone as a Driver of Cognitive Resilience
Recipient
University of California, San Francisco
Award Amount
$451,000.00
Ceiling
$451,000.00
Awarded
August 17, 2026
Identifier
1R21AG104396-01
NIH awarded a multiyear grant to University of California, San Francisco to study the steroid hormone ADIOL's role in cognitive resilience and aging, aiming to develop therapies for Alzheimer's disease.
Description
This project investigates a naturally occurring steroid hormone, androst-5-ene-3β,17β-diol (ADIOL), as a potential regulator of cognitive capacity in mammals. The research aims to understand how ADIOL supports learning and memory in mice and its relationship with human cognitive aging. The project builds on discoveries in C. elegans, where elevating ADIOL levels enhances learning and memory, including in aged animals. The study explores ADIOL's mechanism of action through estrogen receptor beta (ERβ) and its role in suppressing kynurenine pathway (KP) metabolites, which are linked to cognitive deficits in mammals. In mice, systemic ADIOL treatment accelerates learning in Pavlovian conditioning tasks. The project will utilize ERβ pharmacology, fiber photometry, and two-photon calcium imaging to determine neural mechanisms. Additionally, the project will analyze plasma samples from 80 adults aged 40–79 from the UCSF Hillblom Brain Aging Cohort to measure ADIOL, related steroids, and KP metabolites. The goal is to uncover steroid-based mechanisms to enhance cognitive healthspan and reduce vulnerability to Alzheimer’s disease and related dementias.