# The Wake Forest Nonhuman Primate Radiation Survivor Cohort

> **NIH NIH U01** · WAKE FOREST UNIVERSITY HEALTH SCIENCES · 2022 · $387,500

## Abstract

Project Summary
This supplemental application seeks funding to explore the potential shared neurodegenerative mechanisms
between Alzheimer's Disease (AD) and radiation-induced brain injury (RIBI) in aging nonhuman primates
(NHP; here rhesus macaques, Macaca mulatta) through a multi-investigator, multidisciplinary collaborative
effort involving functional Positron Emission Tomography (PET) neuroimaging, neuropathology, and molecular
biomarkers of neuropathology in brain and cerebrospinal fluid. This project will leverage the substantial existing
investment of NIH in the NIAID-sponsored Wake Forest Non-Human Primate Radiation Survivor Cohort. This
work is within the scope of the original application's goal of "to identify and study relevant patterns of post-
irradiation morbidity and mortality in a unique, controlled, well-defined NHP population, by collaborating and
sharing data with NIH-funded and other federally-funded investigators". This supplemental application is
focused on Alzheimer's Disease and related dementias. The proposed work requires additional funding for (1)
PET imaging of NHP brains to quantitatively assess amyloid and tubulin in vivo; (2) gold-standard
neuropathology assessments including immunohistochemistry for amyloid beta and phospho-tau proteins; and
(3) molecular studies of key biomarkers of neurodegenerative processes in brain tissue and cerebrospinal fluid.
For Aim 1 animals will be assessed by neuroimaging in vivo, including age matched subsets with and without
prior exposure to total body irradiation. For Aims 2 and 3, we will assess archived brain and CSF samples from
control and TBI subjects which have already gone to necropsy and from subjects in Aim 1 which come to
necropsy. We hypothesize that there will be both common and divergent mechanisms underlying age-
associated AD-like pathology and the neuropathologic injury of RIBI. The proposed work will contribute to our
basic understanding of vascular, inflammatory, and degenerative processes in chronic age and radiation-
related pathologies of the primate brain. The studies will lead to publications and future grant applications to
understand accelerated neurodegeneration in irradiated nonhuman primates and potential relationships within
the amyloid/tau/neurodegeneration + vascular (ATN+V) framework of AD.

## Key facts

- **NIH application ID:** 10499118
- **Project number:** 3U01AI150578-03S1
- **Recipient organization:** WAKE FOREST UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** J. MARK CLINE
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $387,500
- **Award type:** 3
- **Project period:** 2020-08-01 → 2027-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10499118

## Citation

> US National Institutes of Health, RePORTER application 10499118, The Wake Forest Nonhuman Primate Radiation Survivor Cohort (3U01AI150578-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10499118. Licensed CC0.

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