# RAGE, mitochondria, and tau pathology in AD

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $594,211

## Abstract

PROJECT SUMMARY/ABSTRACT
Mitochondrial and synaptic dysfunction is early pathological features of the Alzheimer's disease (AD)-affected
brain. Perturbed bioenergetics function, respiration failure, aberrant mitochondrial dynamics, and increased
levels of reactive oxygen species (ROS) are observed in brains and peripheral tissues including platelets of
subjects with AD. RAGE (Receptor for Advanced Glycation Endproducts, AGEs) functions as a signal
transducing cell surface acceptor site for AGEs, S100/calgranuline, or amyloid-beta peptide (Aß). Interaction of
RAGE and its ligands increases oxidative stress, inflammation, Aβ accumulation, and impairs synaptic function
and learning memory. However, the impact of RAGE on tau- and Aβ-mediated mitochondrial stress, tau
pathology, tau-induced synaptic and cognitive dysfunction in AD remains unclear. It is unclear whether and how
RAGE-dependent signal transduction contributes to alterations in mitochondrial structure and function in AD.
The proposed studies will test the hypothesis that RAGE functions as signal transduction to perturb mitochondrial
structure and function, and oxidative stress, leading to synaptic mitochondrial and synaptic dysfunction. This
proposal will address the fundamental questions of whether RAGE is a key player in AD-related aberrant
mitochondria and synaptic injury and whether blockade of RAGE restores mitochondrial and neuronal function.

## Key facts

- **NIH application ID:** 10320076
- **Project number:** 5R01AG061324-04
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** SHI FANG YAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $594,211
- **Award type:** 5
- **Project period:** 2019-02-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10320076

## Citation

> US National Institutes of Health, RePORTER application 10320076, RAGE, mitochondria, and tau pathology in AD (5R01AG061324-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10320076. Licensed CC0.

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