# The effects of iron on oxidative stress and Alzheimer's biomarkers in amyloid-positive and negative elderly normal

> **NIH NIH R01** · WEILL MEDICAL COLL OF CORNELL UNIV · 2024 · $443,514

## Abstract

PROJECT ABSTRACT/SUMMARY
 Alzheimer's disease (AD) is the most common cause of dementia. Beta-amyloid plaques in the brain
on autopsy are one of the key pathological hallmarks of AD, but numerous clinical trials targeting beta-amyloid
have failed. Many studies in brain specimens and animal models of AD have shown that iron is found in and
adjacent to beta-amyloid plaques and may contribute to neuronal injury. People with evidence of beta-amyloid
plaques on positron emission tomography (PET) and high levels of brain iron have accelerated cognitive
decline. However, the mechanisms linking iron to cognitive decline in humans remain unclear. Elucidating
these mechanisms is critical for the development of potential iron-targeted therapies. The objective of this
proposal is to use state-of-the-art magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) markers of
iron, oxidative stress, and neuronal injury to understand the link between iron and AD. If successful, this
proposal will clarify iron's role as a potential key upstream target in therapeutic trials to slow or stop the
development of AD. This application is for a prospective study of 80 elderly normal individuals, half of whom
will have PET evidence of cerebral amyloid deposition. The first aim is to test the hypothesis that subjects with
cerebral amyloid deposition will have higher baseline levels of brain iron and higher rates of iron accumulation,
using quantitative susceptibility mapping, a noninvasive MRI measure of brain iron. The second aim is to test
the hypothesis that subjects with cerebral amyloid deposition will have higher baseline levels of oxidative
stress and higher rates of increase in oxidative stress, as reflected by lower glutathione levels on proton MR
spectroscopy and higher isoprostane levels in the CSF. The third aim is to test the hypothesis that subjects
with cerebral amyloid deposition will have greater baseline evidence of AD biomarkers and longitudinal change
in AD biomarkers, including CSF markers of beta-amyloid, tau, and hyperphosphorylated tau, brain atrophy
and cortical thinning, and memory decline. The results of this proposal will advance our understanding of the
role of iron in AD pathogenesis and as a potential therapeutic target for clinical trials.

## Key facts

- **NIH application ID:** 10840391
- **Project number:** 5R01AG068398-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** GLORIA Chia-Yi CHIANG
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $443,514
- **Award type:** 5
- **Project period:** 2020-08-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10840391

## Citation

> US National Institutes of Health, RePORTER application 10840391, The effects of iron on oxidative stress and Alzheimer's biomarkers in amyloid-positive and negative elderly normal (5R01AG068398-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10840391. Licensed CC0.

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