The University of Kentucky led a 22-person team that used gene editing to convert an Alzheimer’s risk form of the APOE gene to a protective form in living mice. Treated animals showed reduced amyloid plaques, lower inflammation and improved memory, even when the switch occurred later in life. The study, published in Nature Neuroscience, is an important proof of concept, but developing a safe, effective human therapy will require years of additional work to resolve delivery, timing and safety trade-offs.
Kentucky Researchers Convert Alzheimer’s Risk Gene to Protective Form in Mice — A Promising Proof of Concept
The University of Kentucky led a 22-person team that used gene editing to convert an Alzheimer’s risk form of the APOE gene to a protective form in living mice. Treated animals showed reduced amyloid plaques, lower inflammation and improved memory, even when the switch occurred later in life. The study, published in Nature Neuroscience, is an important proof of concept, but developing a safe, effective human therapy will require years of additional work to resolve delivery, timing and safety trade-offs.
05:44 PM, 11/21/2025Health
Scientists at the University of Kentucky and collaborators have for the first time edited a gene in living mice to convert a version linked to higher Alzheimer’s risk into a protective form. The work, led by a 22-person team and published in Nature Neuroscience, reduced amyloid plaque accumulation and inflammation and improved memory performance in treated animals.
How the experiment worked
The team focused on the apolipoprotein E (APOE) gene, which exists in closely related variants known as E2, E3 and E4. Researchers engineered mice to carry the higher-risk variant and then delivered a drug-like gene-editing treatment that prompted the animals’ DNA to switch from producing the risk form to producing the protective form.
Lead author Lesley Golden said the model lets researchers observe what happens when an organism moves from genetic risk to resilience: “Remarkably, even switching the gene later in life improved multiple aspects of Alzheimer’s pathology at once.”
Key findings and limitations
The treated mice showed fewer Alzheimer’s-like brain changes, including reduced amyloid plaque buildup and lower inflammation, and they performed better on memory tests. Lance Johnson, an associate professor in the UK College of Medicine’s Department of Physiology, described the work as an exciting proof of concept for targeting APOE.
Important caveats remain. Mice do not naturally develop Alzheimer’s disease, so researchers used a genetic model that produces the amyloid plaques seen in the human condition. The gene conversion in mice took only days, but similar editing in humans would likely take much longer and faces major obstacles: safe and efficient delivery, correct timing, long-term safety, and precise control over editing outcomes.
Safety trade-offs and next steps
Any potential human application must weigh benefits against other health risks. Johnson noted that the APOE variant that protects against Alzheimer’s (E2) can increase risk for other conditions, such as age-related macular degeneration and some cardiovascular problems. Scientists will need to ensure treatments don’t reduce Alzheimer’s risk while increasing other health risks.
At best, a reliable and safe human gene-editing therapy is years away. The team hopes to continue the work pending further funding and extensive preclinical and clinical testing.
Local context
The research brings hope to many families: the Alzheimer’s Association’s 2025 report estimates tens of thousands of older adults and many unpaid caregivers in states such as Kentucky are affected by the disease. While this study is not a cure, it points to a future strategy that could, in theory, prevent large numbers of cases if safety, delivery, and ethical challenges can be resolved.
Bottom line: This is a compelling early demonstration that converting a high-risk APOE variant into a protective form can reduce Alzheimer’s-like pathology in mice. Substantial scientific, logistical, and safety hurdles must be cleared before considering human trials.