# Longitudinal Cognitive and Behavioral Testing and Immunohistochemical Assessment of Alzheimer's Disease Markers, Immune Response, Neurogenesis, and Cell Loss in a Natural Aging Primate Model

> **NIH NIH R15** · CARLETON COLLEGE · 2021 · $438,067

## Abstract

Project Summary
The broad objective of this research is to study the relationship between particular cognitive
events, specifically failure in working memory, attention, and executive function, and particular
biological events, specifically amyloid beta (Ab) accumulation, tau deposits, immune reactivity in
glial cells, neurogenesis, and cell loss, in an aging nonhuman primate model. One specific aim
is to develop a set of cognitive tasks that can be used with nonhuman primates to reveal age-
dependent losses and to differentiate those from losses emerging from neuropathological
conditions. Individuals of a specific species, the cotton top tamarin, are tested in 3 cognitive
tasks that have been found to separate unique differences in aging and Alzheimer's disease
(AD) in humans. The three tasks developed for primates have been used extensively with
humans with high replicability over studies. Differences between elderly human controls and AD
patients emerge in tests of immediate forgetting, visuospatial attention, and failures in rule-
shifting. The memory task employed in this current project, delayed matching-to-sample, has
also been used extensively in comparative cognition with highly consistent results. A visual
search task, which has been used both to study humans and other animals, is also employed. A
version of the Dimensional Change Card Sort (DCCS) task is created to test flexibility in rule
shifting in monkeys. Tamarins are tested daily in short sessions in each task through the end of
a natural aging process, and then assessed post mortem by immunohistochemical techniques
to estimate the AD markers Ab and hyperphosphorylated tau, glial reactivity, neural death, and
neurogenesis. A second specific aim is to determine whether these biological events correlate
with age and reveal a particular neural signature that would explain cognitive failures that
subjects expressed near the end of life. Disease-modifying treatments for dementia and AD will
emerge from understanding how changes in the neural environment induce failures in cognition
and attention. Tamarins have demonstrated Ab accumulation in an age-dependent fashion
similar to humans, and cognitive, perceptual, and social thinking and cooperative breeding
comparable in unique ways to humans. Another goal is to provide biological and cognitive data
from a species closely related to the common marmoset, another species in the Callitrichidae
primate family which is becoming a prominent model in AD and aging research. The tamarin
model is tested as they naturally age, with results from tasks that typically differentiate AD from
aging in humans, and correlated with biological events used to diagnose AD in humans.

## Key facts

- **NIH application ID:** 10111648
- **Project number:** 2R15AG051940-02
- **Recipient organization:** CARLETON COLLEGE
- **Principal Investigator:** JULIE J NEIWORTH
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $438,067
- **Award type:** 2
- **Project period:** 2017-03-15 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10111648

## Citation

> US National Institutes of Health, RePORTER application 10111648, Longitudinal Cognitive and Behavioral Testing and Immunohistochemical Assessment of Alzheimer's Disease Markers, Immune Response, Neurogenesis, and Cell Loss in a Natural Aging Primate Model (2R15AG051940-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10111648. Licensed CC0.

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