How different forms of tau protein harm brain networks in Alzheimer's
Project 3: Roles of Tau Levels, Sequence and Interactors in Neural Network Dysfunction of Alzheimer's Disease
Researchers are comparing how different versions and amounts of the brain protein tau change nerve-cell networks in people with Alzheimer's disease.
Quick facts
| Grant type | P01 program project |
|---|---|
| Study type | NIH-funded research |
| Funding institution | J. David Gladstone Institutes NIH-funded |
| Lab location | 1 site (San Francisco, United States) |
| Project ID | NIH-11166576 on NIH RePORTER |
What this research studies
The team will create new mouse models that combine human amyloid, the Alzheimer risk gene APOE4, and three forms of human tau: the common (wildtype) form, the A152T variant linked to higher Alzheimer risk, and the P301S mutation used in other dementia models. They will measure brain function, pathology, and gene activity across these models to see which tau types cause the most network disruption. Experiments include recordings of neuronal activity, detailed tissue pathology, and transcriptomic analyses to map molecular changes tied to dysfunction.
Who could benefit from this research
Good fit: People living with Alzheimer's disease, those with mild cognitive impairment, or individuals at higher genetic risk (for example APOE ε4 carriers) would be most likely to benefit from findings and could be future trial candidates.
Not a fit: People without Alzheimer's pathology or whose cognitive problems are driven by non-tau mechanisms may not receive direct benefit from this work.
Why it matters
Potential benefit: If successful, this work could pinpoint which forms of tau drive Alzheimer's-related brain dysfunction and guide more targeted treatments or diagnostics.
How similar studies have performed: Previous animal models, especially those using the P301S tau mutation, have taught us much but do not fully mimic typical Alzheimer's, so comparing near-physiological tau forms in an amyloid/APOE4 context is a relatively new approach.
Where this research is happening
San Francisco, United States
- J. David Gladstone Institutes — San Francisco, United States (Active)
Researchers
- Principal investigator: Mucke, Lennart — J. David Gladstone Institutes
- Study coordinator: Mucke, Lennart
About this research
- This is an active NIH-funded research project — typically early-stage science, not a clinical trial accepting patient enrollment.
- Some NIH-funded labs run parallel clinical studies or seek volunteers for related work. To check, contact the principal investigator or institution listed above.
- For full project details, budget, and progress reports, visit the official NIH RePORTER page below.