How Alzheimer's proteins disrupt brain circuits during normal behavior

Neural Circuit Disruption in Freely-Behaving models of Alzheimer's Disease.

NIH-funded research Massachusetts General Hospital · NIH-11321610

Researchers are tracking brain cell activity in mouse models that carry human Alzheimer’s genes to see how amyloid and tau change neurons during everyday behavior.

Quick facts

Grant typeR01 grant
Study typeNIH-funded research
Funding institutionMassachusetts General Hospital NIH-funded
Lab location1 site (Boston, United States)
Project IDNIH-11321610 on NIH RePORTER

What this research studies

Using tiny head-mounted microscopes and multi-electrode recordings, the team will watch calcium signals and brain rhythms in freely moving mice. They will compare a classic early-onset model (APP/PS1) with a newer model that has humanized APP plus APOE4 and TREM2 risk variants to mimic late-onset Alzheimer’s. The project looks at how amyloid and tau affect neuronal activity across different behavioral states to understand when circuits go awry. Results aim to link molecular changes to real-time circuit dysfunction that matters for memory and behavior.

Who could benefit from this research

Good fit: Although the research is done in mice, people living with Alzheimer’s disease or who carry high-risk genes like APOE ε4 are the groups most likely to benefit from the findings in the long run.

Not a fit: Because the project studies animal models and does not enroll patients, there is no direct treatment benefit for people now, and those without Alzheimer’s-related pathology are unlikely to gain near-term benefit.

Why it matters

Potential benefit: This could reveal when and where Alzheimer’s proteins disrupt brain networks, pointing to better times and targets for future therapies.

How similar studies have performed: Previous studies in anesthetized amyloid models have shown abnormal neuronal firing and calcium overload, but applying miniaturized microscopes in freely moving animals and in humanized late-onset models is a newer approach.

Where this research is happening

Boston, 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.