How the brain enzyme gamma‑secretase makes amyloid in Alzheimer's
Official title: Structure and Function of Gamma-Secretase in Alzheimer's Disease
Funded at University of Kansas Lawrence · NIH-11304877 · Data updated 2026-11-12
This project explains how the gamma‑secretase enzyme produces different forms of amyloid protein that can drive Alzheimer's disease in people.
Quick facts
| Grant type | R01 grant |
|---|---|
| Study type | NIH-funded research |
| Funding institution | University of Kansas Lawrence NIH-funded |
| Lab location | 1 site (Lawrence, United States) |
| Project start | May 1, 2020 |
| Project end | December 31, 2030 |
| Funding year | 2026 |
| Award (this year) | $643,210 |
| NIH project number | 2R01AG066986-06A1 |
| Project ID | NIH-11304877 on NIH RePORTER |
Who could benefit from this research
✓Could help
This research is most relevant to people with Alzheimer's disease, especially those with early‑onset familial cases caused by APP or presenilin (PSEN1) mutations.
✕Less likely to help
People whose dementia is driven by non‑amyloid causes or who are in very advanced stages of disease may be less likely to see direct benefits in the near term.
What this research studies
I want to understand how gamma‑secretase cuts the APP protein to make different lengths of amyloid beta, including the harmful Aβ42 linked to Alzheimer's. The team studies how inherited mutations in APP and presenilin change the enzyme's activity and cause the enzyme and its substrate to become stalled together. They use biochemical and structural methods to observe the enzyme at the molecular level and trace how long amyloid pieces are trimmed into shorter ones. The goal is to explain why some mutations increase production of the most toxic amyloid forms.
Why it matters
Potential benefit: If successful, this work could point to ways to prevent production of the most harmful amyloid forms and guide safer, more precise Alzheimer's treatments.
How similar studies have gone: Prior studies have linked presenilin mutations and gamma‑secretase structure to altered amyloid production, but therapies targeting gamma‑secretase have had mixed clinical results and better mechanistic insight is still needed.
Where this research is happening
-
University of Kansas Lawrence
Lawrence, United States Active
Researchers
- Principal investigator: Wolfe, Michael S — University of Kansas Lawrence
- Study coordinator: Wolfe, Michael S
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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.