# Comparative genomics of longevity. Supplement: Establishing degu as a new animal model for Alzheimer's disease.

> **NIH NIH P01** · UNIVERSITY OF ROCHESTER · 2020 · $385,000

## Abstract

Summary
 The overarching goal of our Program Project Grant (PPG) is to understand the mechanisms of
aging and longevity by using comparative biology approach. The four projects within the PPG are
investigating mechanisms of longevity using a collection of 18 rodent species with lifespans ranging
from 3 to 32 years and widely divergent susceptibility to age-related diseases.
 Here we would like to expand our research into Alzheimer’s disease (AD) related dementias by
developing Octodon degus (degu) as a new research model for the studies of AD. Degu is a rat-sized
social rodent native to Chile. Degus are relatively long-lived with the maximum-recorded lifespan of 14
years. Remarkably, after age of 3, degus develop AD pathology that closely resembles the human
condition. Aged degus begin to show cognitive impairment, their brains accumulate amyloid beta (Aβ)
and tau deposits and display neuroinflammation. Furthermore, degu Aβ is much closer in sequence, to
the human protein, differing by only one amino acid, than Aβ of mouse or rat. As degus are social
animals, they display behaviors that can be used to monitor the progression of cognitive decline.
 Building on our experience establishing colonies of naked mole rats at the University of
Rochester we have successfully established breeding colonies of degu. Our goal is to establish degu
as a model for AD research. As it is still unclear what factors are important for development and
resolution of AD, we propose the following aims: (1) test the role of type 2 diabetes mellitus in the
neurodegeneration phenotype seen in the animals. Importantly, AD pathology in degu seems to be
linked to high glycemic diet, which provides a good model for development of AD in humans; (2)
interrogate transcriptomics and proteomics of different cell types in specific brain areas of the
animals to better understand the susceptibilities of these areas to neurodegeneration and to
identify modifiable factors.
 Many AD drugs that showed promise in transgenic mouse models failed in human trials,
suggesting that the mouse models do not replicate key aspects of AD pathogenesis. Transgenic mice
express mutant versions of human proteins that promote local Aβ overproduction. However, the key
processes and genes involved in sporadic AD are still unresolved. Importantly, unlike other disease
models, in degus we can interrogate the role of whole organismic processes in the development of the
disease. Degus will provide the research community with a natural model for sporadic AD that can be
used to find efficient therapeutic targets, test interventions before they are applied to humans, and to
identify early disease biomarkers. This novel model has the potential to have strong impact on the field.

## Key facts

- **NIH application ID:** 10123549
- **Project number:** 3P01AG047200-07S2
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Vera Gorbunova
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,000
- **Award type:** 3
- **Project period:** 2014-05-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123549

## Citation

> US National Institutes of Health, RePORTER application 10123549, Comparative genomics of longevity. Supplement: Establishing degu as a new animal model for Alzheimer's disease. (3P01AG047200-07S2). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10123549. Licensed CC0.

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