# Development of an Innovative Vervet (Chlorocebus aethiops sabaeus) Model of Early Alzheimer's-like Neuropathology and Symptomatology

> **NIH NIH R24** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $1,305,223

## Abstract

This application is in response to RFA-AG-21-003: New/Unconventional Animal Models of Alzheimer’s Disease
(AD). Currently available animal models of AD mostly model the less common early-onset familial AD and have
poor predictive value in clinical trials. However, nonhuman primates are useful for studying characteristics of
the more clinically relevant late-onset sporadic AD because of their phylogenetic similarity to humans in brain
structure and function; complex endocrine, social, and cognitive characteristics; large size favorable for
imaging studies and cerebrospinal fluid collection; and sequence homology with humans for both tau and Aβ
beta-amyloid (Aβ). Vervets show age-related brain changes similar to humans, including increased Aβ plaque
burden, cognitive and motor deficits, increased AD biomarkers in cerebrospinal fluid, paired helical filament tau
(PHF-tau) formation, decreased brain volumes, decreased cerebral glucose utilization, and altered cortical
transcription profiles. NHPs require further study to understand their apparent resistance to developing
extensive neurofibrillary tangles which may provide insight into mechanisms underlying resilience, to
characterize central nervous system tau species, and to develop PET tracers for Aβ and other targets
associated with AD and dementia .Modifiable risk factors that are potential targets for early intervention in
humans include obesity, hypertension, physical activity, impaired glucose tolerance, psychosocial stress, and
poor sleep. Vervets respond to stress like humans and may become obese. Age increases their rates of
hypertension and impaired glucose tolerance accompanied by decreased Aβ42/Aβ40 in cerebrospinal fluid.
Thus, vervets may provide opportunities for translational and mechanistic research highly relevant to late-onset
sporadic AD. The premise of the proposed research is that vervets are a promising model of late-onset
sporadic AD in which AD-related disease progression could be characterized and altered by early intervention
on modifiable risk factors. The overarching goal is to further develop, characterize, and validate the vervet
model of neuropathology and cognitive decline, while identifying novel targets for early intervention for AD
characteristics. Our Specific Aims are to determine age-related changes in cognitive and physical function,
cerebrospinal fluid and imaging biomarkers; identify targets for early intervention by characterizing modifiable
risk factors for late-onset sporadic AD; and assess the predictive validity of these risk factors for
neuropathology in 30 vervets from our Vervet Research Colony (from 10 to 30 years old) which comprise the
Aging Vervet Cohort. Unique resources at Wake Forest that will assure rapid progress toward our goal include
our Alzheimer’s Disease Research Center; Aging Vervet Cohort, extensive Biospecimen, Data and Image
Repository, unique nonhuman primate imaging capabilities, expertise in nonhuman primate research, and
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## Key facts

- **NIH application ID:** 10483200
- **Project number:** 5R24AG073199-02
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SUZANNE CRAFT
- **Activity code:** R24 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,305,223
- **Award type:** 5
- **Project period:** 2021-09-15 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10483200

## Citation

> US National Institutes of Health, RePORTER application 10483200, Development of an Innovative Vervet (Chlorocebus aethiops sabaeus) Model of Early Alzheimer's-like Neuropathology and Symptomatology (5R24AG073199-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10483200. Licensed CC0.

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