# Alzheimer's Disease Pathology and Biomarkers in a Cohort of Aged Rhesus Macaques

> **NIH NIH P51** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2024 · $312,989

## Abstract

Alzheimer’s Disease (AD) represents a major public health concern, affecting more than 5.7 million Americans and
being the fifth leading cause of death among individuals aged 65 and over. Despite recent progress made through
the advent of amyloid-beta (AB)-targeting immunotherapies, AD remains incurable, highlighting the urgent need
for improved animal models and biomarkers that recapitulate the key processes underlying AD pathogenesis. Non-
human primates (NHPs) are prime candidates to fulfill this role, thanks to their phylogenetic proximity, long lifespan,
highly differentiated prefrontal cortex, and sophisticated behavioral repertoire, which has greatly contributed to our
understanding of cognitive aging. However, the use of this vital animal model is still limited by the lack of tools to
investigate synaptic health, neuroinflammation, and AD-like pathology in vivo. Fluid biomarkers are powerful tools
in clinical settings, yet the effectiveness of fluid biomarkers in monitoring age-related brain changes in NHPs is
almost entirely unknown. We have recently demonstrated the utility of CSF biomarkers in monitoring pathology
progression in middle-aged animals that received experimental interventions to induce aspects of AD pathology
(Beckman et al., 2019; Beckman et al., 2021), but the dynamics of CSF biomolecules in both healthy and
pathological brain aging remain entirely unknown. With support from the parent award, a large biobank of geriatric
NHP samples has been established at the CNPRC. We propose, therefore, to biochemically and
neuropathologically characterize AD-like pathology and neuroinflammation in this cohort of geriatric macaques and
correlate those findings to the levels of CSF and plasma biomarkers. Upon successful completion of this project,
we will have new tools to identify candidate NHP subjects for aging- and dementia-focused studies and a method
to monitor the occurrence and progression of brain aging and pathology in rhesus macaques across all National
Primate Research Centers. We will test the following hypotheses through 3 Specific Aims. Hypothesis 1: We
hypothesize that, by employing a large cohort of aged Rhesus macaques of both sexes, we will be able to observe
multiple trajectories of AD-like pathology, including distinct patterns of amyloid plaque burden and tau
hyperphosphorylation, which may have been too subtle to be detected in previous NHP studies. Hypothesis 2:
We hypothesize that AD-like pathology in aged Rhesus macaques will be associated with a unique pattern of
neuroinflammatory markers compared to healthy aged subjects. Hypothesis 3: We hypothesize that multiple
human core AD and neuroinflammation biomarkers will be altered in the plasma and CSF of aged Rhesus
macaques, and these alterations will be correlated with the degree of AD-like pathology in the brain of these animals
in an age- and sex-dependent manner.

## Key facts

- **NIH application ID:** 10937930
- **Project number:** 3P51OD011107-63S1
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** Simon J. Atkinson
- **Activity code:** P51 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $312,989
- **Award type:** 3
- **Project period:** 1997-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10937930

## Citation

> US National Institutes of Health, RePORTER application 10937930, Alzheimer's Disease Pathology and Biomarkers in a Cohort of Aged Rhesus Macaques (3P51OD011107-63S1). Retrieved via AI Analytics 2026-06-01 from https://api.ai-analytics.org/grant/nih/10937930. Licensed CC0.

---

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