How changes in NOTCH3 affect brain blood vessel disease

Advanced conformational changes in NOTCH3 and cerebrovascular disease severity

NIH-funded research Veterans Health Administration · NIH-11213915

Researchers are looking at whether specific changes in the NOTCH3 protein are linked to worse brain blood vessel disease and higher dementia risk, especially among Veterans.

Quick facts

Grant typeNIH-funded research
Study typeNIH-funded research
Funding institutionVeterans Health Administration NIH-funded
Lab location1 site (Ann Arbor, United States)
Project IDNIH-11213915 on NIH RePORTER

What this research studies

If you take part, researchers will study specific changes in the NOTCH3 protein that are known to cause CADASIL and other blood vessel problems in the brain. They will test patient samples for forms of NOTCH3 with multiple reduced cysteines and for a small released piece called the N-terminal fragment (NTF). The team will combine lab-based protein analyses with clinical information and imaging to connect these molecular signs to how severe vessel disease and cognitive symptoms are. The goal is to find markers or targets that could help detect or slow vascular contributions to dementia.

Who could benefit from this research

Good fit: People with CADASIL or known NOTCH3 mutations, and patients with vascular cognitive impairment or mixed Alzheimer’s and vascular disease (especially Veterans), are the most relevant candidates.

Not a fit: People whose cognitive problems are due solely to non-vascular causes unrelated to NOTCH3 are less likely to benefit directly from this work.

Why it matters

Potential benefit: If successful, this work could lead to new biomarkers or treatments that detect or protect against brain blood vessel damage that speeds dementia.

How similar studies have performed: This builds on prior CADASIL research but the specific NOTCH3 cleavage and the NTF fragment are relatively new findings and have not yet been developed into clinical tests or treatments.

Where this research is happening

Ann Arbor, 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.
Conditions Alzheimer disease dementiaAlzheimer syndrome
Last reviewed 2026-06-15 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.