Targeting mitochondrial complex I to protect the brain in Alzheimer’s

Mitochondrial Complex I as a Target for Neuroprotection in AD

NIH-funded research Mayo Clinic Rochester · NIH-11297715

This project tests whether small doses of drugs that mildly block a part of the cell’s energy machinery (mitochondrial complex I) can protect brain cells and help people with Alzheimer’s disease.

Quick facts

Grant typeNIH-funded research
Study typeNIH-funded research
Funding institutionMayo Clinic Rochester NIH-funded
Lab location1 site (Rochester, United States)
Project IDNIH-11297715 on NIH RePORTER

What this research studies

Researchers are using drugs that partially inhibit mitochondrial complex I in animal models of Alzheimer’s to trigger protective stress responses in brain cells. They treat mice after memory problems begin and measure inflammation, brain energy use, protein markers linked to Alzheimer’s (amyloid and tau), synaptic function, and behavior. The team also compares the pathways affected in mice with human brain gene-expression data from the AMP-AD database to see if the same mechanisms matter in people. This work aims to show whether the approach is both effective and safe enough to consider moving toward human testing.

Who could benefit from this research

Good fit: Ideal candidates would be people living with Alzheimer’s disease or those at increased genetic risk (for example, APOE-ε4 carriers) who are interested in new therapeutic approaches.

Not a fit: People whose cognitive problems are from non-Alzheimer’s causes or who have advanced frailty or severe medical comorbidities may not benefit from this approach.

Why it matters

Potential benefit: If successful, this approach could slow or stop neurodegeneration and preserve memory and brain function in people with Alzheimer’s disease.

How similar studies have performed: Previous preclinical studies in multiple familial mouse models showed reduced inflammation, lower amyloid and tau pathology, and improved cognition with partial complex I inhibition, but testing in humans is still novel.

Where this research is happening

Rochester, United States

Researchers

About this research

  1. This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
  2. Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
  3. For full project details, budget, and progress reports, visit the official NIH RePORTER page below.
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.