Study finds one copy of protective genetic variant helps stave off early-onset Alzheimer's disease

### Protective Genetic Variant Delays Early-Onset Alzheimer's Disease

**Summary:**

Recent research has revealed that a single copy of the APOE3 Christchurch genetic variant can delay the onset of Alzheimer's disease in individuals at high risk. This study focused on a Colombian family of around 6,000 members, who are prone to early-onset Alzheimer's in their 40s due to the 'Paisa' (Presenilin-1 E280A) mutation. The study builds on a 2019 report of a woman from this family with two copies of the Christchurch variant, who delayed Alzheimer's symptoms until her 70s. This new evidence confirms that even one copy of the variant provides some protection, bolstering the potential for targeting this genetic pathway in therapeutic developments.

**Full Story:**

A scientific investigation that started with a remarkable patient has now expanded significantly. In 2019, researchers from Mass General Brigham hospitals—Mass Eye and Ear and Massachusetts General Hospital (MGH)—documented a patient who did not exhibit cognitive impairment until her late 70s, despite her family's high genetic risk for early-onset Alzheimer's disease. This patient carried two copies of the rare APOE3 Christchurch variant. The recent study extends these findings to 27 additional family members who possess just one copy of this variant and also experienced delayed onset of the disease.

Published in The New England Journal of Medicine, this study provides the first evidence that a single copy of the Christchurch variant can offer some level of protection against autosomal dominant Alzheimer's disease, albeit less than having two copies. These findings are significant for drug development, indicating that targeting this genetic pathway could be beneficial.