How APOE gene types and amyloid beta affect brain network problems in Alzheimer's
Project 2: Co-pathogenic Interactions between ApoE Isoforms and Abeta in Neural Network Dysfunction of Alzheimer's Disease
['FUNDING_P01'] · J. DAVID GLADSTONE INSTITUTES · NIH-11166572
Researchers are looking at how different APOE gene types and amyloid beta together change brain cell connections related to Alzheimer's, using new humanized mouse models.
Quick facts
| Phase | ['FUNDING_P01'] |
|---|---|
| Study type | Nih_funding |
| Sex | All |
| Sponsor | J. DAVID GLADSTONE INSTITUTES (nih funded) |
| Locations | 1 site (SAN FRANCISCO, UNITED STATES) |
| Trial ID | NIH-11166572 on ClinicalTrials.gov |
What this research studies
You will hear about work that uses new knock-in mouse models that carry human versions of amyloid beta, APOE (E2, E3, E4), and tau at normal expression levels to mimic late‑onset and familial Alzheimer's. The team compares how the different APOE isoforms interact with amyloid beta and tau to disrupt neural network function and lead to pathology. Because these mice are humanized without overexpressing transgenes, the researchers aim to observe more realistic disease mechanisms. Findings are intended to explain why some anti-amyloid therapies failed and to point to pathways that might be targeted differently for APOE4 carriers.
Who could benefit from this research
Good fit: People with Alzheimer's disease, those at risk for Alzheimer's (for example APOE4 carriers), or individuals willing to donate samples or join future related trials are the most relevant candidates to follow or benefit from this research.
Not a fit: People without Alzheimer's or whose dementia is driven by non-amyloid mechanisms or who are in very late stages of disease may not see direct benefits from these findings.
Why it matters
Potential benefit: If successful, this work could clarify disease mechanisms and point toward more targeted therapies or trial strategies, especially for people with APOE4.
How similar studies have performed: Previous anti-amyloid clinical trials have largely failed in humans, and while prior animal work linked APOE4 to worse pathology, using humanized knock-in models to map APOE–amyloid–tau interactions is a newer and less-tested approach.
Where this research is happening
SAN FRANCISCO, UNITED STATES
- J. DAVID GLADSTONE INSTITUTES — SAN FRANCISCO, UNITED STATES (ACTIVE)
Researchers
- Principal investigator: PALOP, JORGE J — J. DAVID GLADSTONE INSTITUTES
- Study coordinator: PALOP, JORGE J
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.
Conditions: Alzheimer disease dementia, Alzheimer syndrome