# Novel oxidative pathway targets microglia in Alzheimer's disease

> **NIH NIH R01** · CLEVELAND CLINIC LERNER COM-CWRU · 2024 · $783,003

## Abstract

Abstract
Alzheimer's disease is the most common dementia characterized by progressive cognitive
decline. By estimates, Alzheimer's disease affects more than one-third of the population over 85,
posing a substantial socioeconomic burden. There is an apparent lack of understanding of the
molecular mechanisms of Alzheimer's disease and reported problems with animal models. These
obstacles prevent the development of new therapeutic strategies, especially their translation to
human patients. This proposal is based on molecular and cellular evidence and an analysis of
human Alzheimer's disease cases. It bridges several aspects of Alzheimer's disease pathology:
discovery of unique oxidative stress pathway, new aspects of microglial biology and dysfunction,
and basic mechanisms of cell adhesion/phagocytosis in the context of disease. We will answer
how exactly oxidation causes microglial dysfunction in Alzheimer's disease and how to
prevent/inhibit their detrimental consequences. Based on our pioneering preliminary studies, we
propose that oxidative stress targets important proteins in microglia responsible for phagocytosis,
leading to deficient phagocytosis and microglia overactivation in Alzheimer's disease. Therefore,
we will focus on the mechanisms of this damage and its prevention in Alzheimer's disease and
other neurodegenerative pathologies. We will develop a new intervention approach (compounds
neutralizing oxidative stress) and uncover new specific targets for the treatment of Alzheimer's
disease.

## Key facts

- **NIH application ID:** 10800475
- **Project number:** 1R01AG082382-01A1
- **Recipient organization:** CLEVELAND CLINIC LERNER COM-CWRU
- **Principal Investigator:** Tatiana V Byzova
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $783,003
- **Award type:** 1
- **Project period:** 2024-08-15 → 2029-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10800475

## Citation

> US National Institutes of Health, RePORTER application 10800475, Novel oxidative pathway targets microglia in Alzheimer's disease (1R01AG082382-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10800475. Licensed CC0.

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