Researchers at the University of Bristol have developed a gene-editing technique that may eventually offer a new way to prevent and treat Alzheimer’s disease by altering a key genetic risk factor. The team demonstrated the ability to convert the high-risk APOE4 gene variant into the lower-risk APOE3 variant in human immune cells, a process that could potentially be delivered via a single injection.

Alzheimer’s disease, the most common form of dementia, affects approximately one million people in the United Kingdom, with genetic factors playing a significant role in determining an individual’s risk. The APOE gene, which encodes a protein involved in lipid transport and neuronal health, exists in several variants, with APOE3 being the most common and considered “normal.” In contrast, the APOE4 variant is associated with a markedly increased risk of developing Alzheimer’s. Roughly one in four people carries at least one copy of the APOE4 gene, and possessing two copies can increase the likelihood of developing the disease by up to tenfold compared to the average population.

The difference between APOE3 and APOE4 involves only a single nucleotide change in the gene’s sequence, but this subtle variation significantly affects the protein’s function. The APOE4 protein is thought to contribute to neurotoxicity and impaired clearance of amyloid beta, a protein closely linked to Alzheimer’s pathology.

Using a gene-editing technique that chemically modifies a precise location in the genome, the Bristol team successfully converted APOE4 into APOE3 in immune cells derived from Alzheimer’s patients. A modified virus was used to deliver the corrected genetic material into the cells. Importantly, the researchers found minimal off-target effects on other parts of the genome. According to Dr. Kevin Kemp, associate professor and neuroscientist leading the project, the modified immune cells could potentially enter the brain and release the protective APOE3 protein, which might then be taken up by nerve and other brain cells to counteract the harmful influence of APOE4.

Although these findings have not yet been published in a scientific journal, Kemp anticipates submitting the results for peer review and hopes to initiate clinical trials within five to ten years. The approach could ultimately be applied both as a preventative measure for individuals identified with the APOE4 gene and as a treatment for those exhibiting Alzheimer’s symptoms.

A key challenge for the therapy’s implementation is the limited availability of APOE4 genetic testing through the National Health Service (NHS), which currently offers testing only under specific circumstances, such as a positive family history of dementia. Most individuals learn their APOE status through private tests or research participation.

Experts in the dementia research community emphasize the potential significance of this work in the broader context of emerging disease-modifying therapies. Katharina Cosker, research programmes manager at Alzheimer’s Research UK, noted that addressing genetic risk factors could broaden treatment options, especially for those carrying two copies of APOE4 who may not respond well to existing therapies.

Dr. Richard Oakley, associate director of research and innovation at Alzheimer’s Society, described the findings as an encouraging early step, while cautioning that safety and efficacy in humans remain unproven. With dementia affecting around one million people in the UK, both researchers and advocates underline the urgent need for new treatments that can slow, halt, or prevent the disease.