# Development and Validation of a Marmoset Model of Late-Onset Alzheimer Disease Based on Tau Seeding

> **NIH NIH R24** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2021 · $1,165,318

## Abstract

PROJECT TITLE:
Development and Validation of a Marmoset Model of Late-Onset Alzheimer’s Disease Based on Tau Seeding
PROJECT SUMMARY/ABSTRACT:
 Alzheimer’s disease (AD), the most common cause of dementia, currently afflicts 5.8 million Americans. By
2050, the number of people with AD could reach nearly 14 million. Histopathologically, AD is characterized by
the formation of extracellular aggregates (plaques) of beta-amyloid (Aβ) protein fragments and intracellular
aggregates (neurofibrillary tangles, NFTs) of a hyperphosphorylated form of the microtubule-associated protein
tau (MAPT). Increasing evidence indicates that both Aβ plaques and NFTs begin to accumulate in the brain
decades before symptoms emerge. The long delay between Aβ and tau manifestation and the onset of
memory loss and cognitive decline in AD makes it difficult to properly model AD using short-lived animal
models, such as mice. As age and genetic variation are two of the most significant risk factors for AD, there is
a critical need to develop improved animal models of AD that incorporate genetic variability, aging, and higher-
order cognitive processes that better align with humans. The common marmoset (Callithrix jacchus) is a small
non-human primate (NHP) ideally poised to fill this need. They display social and cognitive behaviors that are
more similar to those of humans. Marmosets live on average 12-13 years and are considered aged at eight
years. Aβ plaques and hyperphosphorylated tau occur naturally in the brain of aging marmosets. Developing
strategies to accelerate the onset of cognitive decline related to the presence of pathological hallmarks of AD
in marmosets would lead to establishing an NHP model with improved translational potential relative to rodent
models. The overall goal of this proposal is to develop and validate an induced marmoset model of late-onset
AD. Converging clinical data indicates that the severity of cognitive impairment in sporadic AD correlates best
with the burden of NFTs. We hypothesize that injecting the brain of aging marmosets with tau will seed the
formation and propagation of NFTs and accelerate the emergence of impairments in a spectrum of AD-related
sensory, motor, cognitive and non-cognitive phenotypes associated with disease progression. We will test this
hypothesis in two aims. In Aim 1, we will use neuronal cell cultures derived from aging marmosets to quantify
the spontaneous presence of AD-related pathology in vitro and evaluate the efficacy of tau seeding strategies
in accelerating the development of NFTs and promoting neurodegeneration and cell death. In Aim 2, we will
seed the brains of aging marmosets with tau, and perform a comprehensive longitudinal evaluation of
functional, behavioral, and clinical biomarkers of AD in the tau-seeded marmosets. This work will lead to the
establishment of a validated NHP model of late-onset AD that will be invaluable in translational research to
elucidate the pathogenic mechanisms of AD and ...

## Key facts

- **NIH application ID:** 10281602
- **Project number:** 1R24AG073190-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** Afonso C Silva
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $1,165,318
- **Award type:** 1
- **Project period:** 2021-08-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10281602

## Citation

> US National Institutes of Health, RePORTER application 10281602, Development and Validation of a Marmoset Model of Late-Onset Alzheimer Disease Based on Tau Seeding (1R24AG073190-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10281602. Licensed CC0.

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