# Establish Mouse Models to Evaluate Androgen Deprivation Therapy on AD

> **NIH NIH R21** · UNIVERSITY OF ALABAMA AT BIRMINGHAM · 2020 · $408,375

## Abstract

Prostate cancer is the most common cancer and the second leading cause of cancer death in American
men. Androgen deprivation therapy (ADT) is a widely applied strategy that can efficiently improve life span and
quality of life for prostate cancer patients. However, recent large-scale epidemiologic studies revealed that
patients with ADT have an increased risk of developing Alzheimer's disease (AD) compared to the general
population, raising a severe public health concern. Age-related androgen depletion has been implicated in the
pathogenesis of neurodegenerative diseases, including AD. However, the role of ADT for prostate cancer in AD
onset and progression has not been clearly defined. Currently, there is no clinically-relevant animal model to
directly examine the effect of ADT on AD development while treating prostate cancer. The primary objective of
this project is to apply powerful mouse genetic approaches to establish a clinically-relevant tumor-bearing AD
model and examine how ADT affects AD onset and progression. We have been studying a genetically
engineered prostate cancer mouse model in which Pten is specifically deleted in prostate using PB-Cre [PB-
Cre;Ptenloxp/loxp, Pten prostate conditional knockout (cKO) mice, referred to as PtencKO]. We found that the PtencKO
line recapitulates prostate cancer features and responses to ADT treatment in human patients. By crossbreeding
this line with a well-established AD model, we expect to create an ideal model to study the interaction between
ADT and AD in the prostate cancer population. We will test the effect of ADT on AD-related cognitive
abnormalities in Aim 1, amyloid-related neuropathological changes in Aim 2, and inflammation/immune
responses in Aim 3. Successfully accomplishing the proposed study will create a unique mouse model that not
only allows us to examine the complex interaction among ADT, AD and prostate cancer, but also may serve as
an invaluable tool for evaluating potential clinical therapies aimed at reducing the negative effects of ADT.

## Key facts

- **NIH application ID:** 10071354
- **Project number:** 1R21AG069436-01
- **Recipient organization:** UNIVERSITY OF ALABAMA AT BIRMINGHAM
- **Principal Investigator:** Lizhong Wang
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $408,375
- **Award type:** 1
- **Project period:** 2020-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10071354

## Citation

> US National Institutes of Health, RePORTER application 10071354, Establish Mouse Models to Evaluate Androgen Deprivation Therapy on AD (1R21AG069436-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10071354. Licensed CC0.

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