# A Squirrel Monkey Model of Alzheimer’s Disease: Developing Behavioral, Blood, and CSF Biomarkers

> **NIH NIH R21** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 2021 · $414,757

## Abstract

Project Summary
Alzheimer’s disease (AD) is a major health concern defined by pathologic changes in the brain that produce
altered behavior and cognitive function. There is a need for primate models of AD because they naturally
recapitulate some neuropathological features of AD with advanced age whereas other model organisms (i.e.,
rodents) do not. For instance, while amyloid-beta (Aβ) deposition occurs in a few mammals, tau-positive
neurofibrillary tangles have only been identified in a very limited nonhuman species studied to date.
Additionally, elderly nonhuman primates, develop cerebral amyloid angiopathy (CAA), a neurovascular
condition found in almost 100% of AD patients and associated with cognitive decline. Here, we are proposing
to further develop squirrel monkeys as a model species for current and future studies on the biology of aging
and AD research. In the R21 component, we propose to train a cohort of group living squirrel monkeys on the
use of an automated cognitive testing system (ACTS) that is designed to assess a variety of cognitive functions
including learning, memory and executive control. Creating large cohorts of squirrel monkeys trained on the
ACTS system will provide animals with established cognitive phenotypes for use in preclinical studies and
allow for examining of their association with potential age-related differences in neuroanatomical,
neuropathological and biomarker data. In the R33 component of the proposed studies, we will test for
associations between age-related changes in cognition and measures of blood/CSF biomarkers, neural
organization and integrity and neuropathology. Additionally, we will test for the effect of ACTS training on
aged related changes in neuroanatomy, neuropathology and AD-related biomarkers. Specifically, during Years
3 to 5, we will obtain magnetic resonance images (MRI) and biological samples from 40 elderly and geriatric
monkeys trained on the ACTS system. With this cohort, 20 monkeys will receive continued cognitive training
(ACTS+) during year 3 to 5 while the remaining 20 individuals will not receive training on any new cognition
asks (ACTS-). In a subset of ACTS+ and ACTS- monkeys, we will obtain postmortem measures of
neuropathology. In one set of analyses within the ACTS cohort, we will test for longitudinal changes in
cognition and their association with variation in (1) neural organization and integrity quantified form MRI
scans and (2) several key biomarkers of AD-related neuropathology. Additionally, to examine whether
cognitive stimulation slows down the normal brain aging process, we will compare age-related changes in
cognition and the brain between the ACTS+ and ACTS- monkeys. The proposed studies, in their entirety, will
fill an important gap in our knowledge about the comparative biology of aging and disease in squirrel monkeys
and provide critical translational insight into how those processes contribute to the progression of CAA and AD
in humans. This information wil...

## Key facts

- **NIH application ID:** 10284696
- **Project number:** 1R21AG073305-01
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **Principal Investigator:** WILLIAM D HOPKINS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $414,757
- **Award type:** 1
- **Project period:** 2021-09-15 → 2024-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10284696

## Citation

> US National Institutes of Health, RePORTER application 10284696, A Squirrel Monkey Model of Alzheimer’s Disease: Developing Behavioral, Blood, and CSF Biomarkers (1R21AG073305-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10284696. Licensed CC0.

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