# Do circulating Anti-Geronic Factors play a protective role in Alzheimer's Disease?

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $405,000

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is a complex neurodegenerative condition that affects millions of individuals worldwide
and currently has no preventative or disease-modifying therapies. Exciting results from heterochronic parabiosis
studies indicate the presence of rejuvenating factors in the circulation that can restore youthful characteristics to
aged cells and tissues, including the restoration of aged neural stem activity and cognitive function. Intriguingly,
heterochronic parabiosis studies have also shown that exposure of transgenic AD model mice to a young
systemic environment results in a marked amelioration of the cognitive deficits and AD-like neuropathology
observed in these animals. The beneficial effects of young blood have been observed in multiple transgenic AD
models. However, the identities of the blood-borne factors that mediate these effects are still unknown. This
proposal is built upon the exciting results emerged from studies funded by R01AG057433, with the goals of
identifying and characterizing circulating anti-geronic factors conserved in mammals, including human, bovine,
and mouse. We found that systemic administration of one of the top candidate anti-geronic factors, PEDF,
significantly improves deficits in cognitive function in aged wild type mice. We hypothesize that conserved
circulating anti-geronic factors such as PEDF mediate the rejuvenation effects of young blood in both aged wild
type animals and transgenic animal models of AD, and that systemic treatment of these factors to an AD mouse
model will improve cognitive function and ameliorate AD-like neuropathology. To test this hypothesis, we will
employ the well-studied 5XFAD transgenic mouse model of AD and will investigate whether and to what extent
top conserved anti-geronic factors exert beneficial effects on cognitive function and AD-like neuropathology in
vivo by measuring changes in amyloid plaque formation, gliosis, synaptic density, cerebrovascular integrity, and
cognitive behavior, as compared to vehicle-treated controls. To understand the mechanisms through which these
factors exerts protective and restorative effects, we will perform single cell RNA-seq analysis to identify the
biological processes and specific cell types mediating their beneficial effects in the brain. Defining the cell type-
specific transcriptional programs that are altered in the brain of the 5XFAD mouse model during the progression
of AD pathology and how these are affected by treatment with anti-geronic factors will provide mechanistic
insights into the protective and restorative effects of youthful blood-borne factors and may identify new
therapeutic targets for AD.

## Key facts

- **NIH application ID:** 10123882
- **Project number:** 3R01AG057433-05S1
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** THOMAS A. RANDO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 3
- **Project period:** 2017-09-15 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123882

## Citation

> US National Institutes of Health, RePORTER application 10123882, Do circulating Anti-Geronic Factors play a protective role in Alzheimer's Disease? (3R01AG057433-05S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123882. Licensed CC0.

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