# Generation, Characterization, and Validation of Marmoset Models of Alzheimer's Disease

> **NIH NIH U19** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2024 · $6,287,895

## Abstract

PROJECT SUMMARY OVERALL
 Alzheimer’s disease (AD) is a devastating neurodegenerative disorder affecting nearly 6 million Americans and
is expected to increase over the next several years. Our limited understanding of the mechanisms that trigger
the emergence of AD has contributed to the lack of interventions that stop, prevent, or fully treat this disease.
We propose to establish the marmoset as the first primate-specific model to reveal the earliest cellular and
molecular events of AD processes and allow charting AD progression from its inception. To do so, we will draw
from a self-sufficient and large colony of research marmosets with dedicated veterinary and husbandry teams,
state-of-the-art in vivo neuroimaging and molecular assays, and a multidisciplinary team of experts in aging
biology, AD genetics and genomics, animal model development and characterization, behavioral and cognitive
phenotyping, and marmoset gene-editing technologies. Our proposal’s overarching goals are to develop
marmoset models of early-onset AD (EOAD) and late-onset AD (LOAD) to enable the investigation of the
underlying cellular and molecular root causes of the pathogenesis and progression of AD and support future
translational studies. We believe that the simultaneous assessment of genetic, molecular, functional, behavioral,
and pathological phenotypes in marmosets will provide translatable knowledge of the origins and progression of
AD in human populations. Furthermore, we posit that the comprehensive study of gene-edited marmoset models
of AD from neurodevelopment through aging will identify emerging phenotypes that precede frank
neuropathology. Our proposal consists of 3 integrated Research Projects that aim to: (1) Conduct
characterization and validation of PSEN1 mutations in marmosets as a model for the study of EOAD, and
investigate early life molecular determinants of AD disease pathogenesis associated with genetic risk for EOAD;
(2) Identify and enhance LOAD-related signatures in outbred and genetically-engineered marmosets; and (3)
Conduct a comparative multimodal phenotypic characterization of marmoset models of AD. These projects will
be supported by 5 Research Cores focused on project administration, bioinformatics, genetic engineering,
multimodal disease characterization, and veterinary and colony management. These supporting cores will
integrate marmoset and human genomic signatures and provide data dissemination and resources to the greater
research community as part of our commitment to open science, generate novel gene-edited marmoset models
of AD, develop optimized protocols for studying disease onset and trajectory in line with clinical protocols,
evaluate therapeutic strategies, and provide specialized animal care and support, respectively, allowing
complete characterization of the marmoset models. At the conclusion of this project, we will have genetically
engineered three AD risk variants into marmoset models, established a disease characterizat...

## Key facts

- **NIH application ID:** 10899732
- **Project number:** 5U19AG074866-03
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Gregory W Carter
- **Activity code:** U19 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $6,287,895
- **Award type:** 5
- **Project period:** 2022-09-01 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10899732

## Citation

> US National Institutes of Health, RePORTER application 10899732, Generation, Characterization, and Validation of Marmoset Models of Alzheimer's Disease (5U19AG074866-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10899732. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*