# Amyloid Beta Oligomer Induction of Alzheimer Disease in Nonhuman Primates

> **NIH NIH R44** · VIRSCIO, INC. · 2020 · $1,119,343

## Abstract

PROJECT SUMMARY
Patients with Alzheimer’s disease (AD) suffer a progressive loss of memory and cognitive ability, and eventual
loss of basic bodily functions and death. The incidence and toll of AD on the healthcare system continues to
rise with significant societal impact. There are no treatments for AD to prevent its inexorable course, and the
principal obstacle to developing new therapies for AD has been the inadequacy of available preclinical
modeling, which almost exclusively involves rodents. Nonhuman primates (NHPs) share greater homology to
humans than rodents in all respects, including genomics, physiology, cognitive processing, neuronal network
complexity and dynamics of drug/target interactions. Given these translational advantages, the long-term goal
of this project is to develop a new NHP model of AD that can be standardized and deployed in rigorous,
reproducible studies to overcome critical current deficiencies in translating preclinical studies into novel clinical
diagnostic strategies and therapies. The objective of this application is to expand and advance our Phase I
work on a NHP model of AD in which intrathecal administration of amyloid β-oligomers (AβOs) induces
increased expression of phosphorylated tau in the medial temporal cortical memory circuit. This finding is
consistent with our overall hypothesis that AβOs will trigger a cascade of accelerated pathology that mimics
the changes occurring in the brains of AD patients. This hypothesis is based on a growing consensus in the AD
research field that AβOs are the toxic species that provoke deposition of the characteristic tangles and plaques
in the brain together with loss of neurons and synapses and associated cognitive decline. The hypothesis will
be tested further in statistically meaningful designs by pursing three specific aims: 1) Determine the extent and
persistence of induced cognitive deficits; 2) Confirm the predictive validity of the model using a
pharmacological intervention, and 3) Assess the utility of EEG recordings from telemetry implants to track
ongoing AD-like pathology. These studies will utilize in-life biomarkers (MRI-determined hippocampal volume,
CSF analytes) together with post-mortem measurements (immunohistochemistry, biochemistry, electron
microscopy) to establish the impact of AβOs administration in the brain of male and female St. Kitts green
monkeys, a species that has been well characterized for its propensity to develop naturally occurring features
of AD pathology. The approach is innovative because it represents a substantial shift from current AD research
paradigms and tests a novel theoretical concept. The research is significant because it is expected to 1)
overcome critical deficiencies in current animal AD models by validating an accelerated, inducible NHP model
of sporadic AD in both males and females, 2) permit effective translation of basic discoveries into novel clinical
diagnostic strategies and therapies, and 3) help understand po...

## Key facts

- **NIH application ID:** 10010401
- **Project number:** 9R44AG067832-02
- **Recipient organization:** VIRSCIO, INC.
- **Principal Investigator:** MICHAEL R WEED
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $1,119,343
- **Award type:** 9
- **Project period:** 2020-09-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10010401

## Citation

> US National Institutes of Health, RePORTER application 10010401, Amyloid Beta Oligomer Induction of Alzheimer Disease in Nonhuman Primates (9R44AG067832-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10010401. Licensed CC0.

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