# Understanding the role of ECSIT in neurodegeneration and Alzheimer's Disease

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2022 · $680,400

## Abstract

PROJECT SUMMARY
Alzheimer’s disease (AD) is the most common form of dementia in humans. Despite intense research there is
as yet no cure for AD and the increasing incidence of AD in developed countries poses a tremendous cost to
society as lifespans increase. There are two forms of AD, those that have genetic determinants and comprise
approximately 5% of cases, and those that arise sporadically, particularly upon aging, and comprise the vast
majority (~95%) of new AD cases diagnosed. The underlying triggers for sporadic AD are diverse and not well
understood. Current therapeutic strategies are limited to those that attenuate AD symptomology without affecting
the progression of the disease itself. Thus understanding the etiology of the disease is necessary to generate
better therapeutics. A widely accepted hypothesis, known as the ‘mitochondrial cascade hypothesis’, posits that
aging leads to accumulation of damaged mitochondria that produce mitochondrial reactive oxygen species
(mROS), triggering progressive oxidative damage that ultimately results in development of AD. However, despite
decades of study, definitive evidence for mROS or aberrant accumulation of damaged mitochondria as a key
trigger have not emerged. Our preliminary studies establish a critical role for the mitochondrial complex I
assembly factor ECSIT in the regulation of mitochondrial function, mROS production, and mitochondrial quality
control. Moreover, we have obtained evidence implicating dysregulation of ECSIT expression/function in AD.
Therefore, we propose a series of experiments that leverage the unique expertise of the two principal
investigators, and institutional capabilities, to fully characterize the role of ECSIT in neurodegeneration and AD.
The proposed experiments will allow us to directly test the mitochondrial cascade hypothesis in murine models
of AD and also probe the relationship between ECSIT dysregulation and the development of AD.

## Key facts

- **NIH application ID:** 10489681
- **Project number:** 5R01AG072660-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** OTTAVIO ARANCIO
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $680,400
- **Award type:** 5
- **Project period:** 2021-09-30 → 2026-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10489681

## Citation

> US National Institutes of Health, RePORTER application 10489681, Understanding the role of ECSIT in neurodegeneration and Alzheimer's Disease (5R01AG072660-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10489681. Licensed CC0.

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