In a new study published in the New England Journal Medicine, researchers focused on two specific genetic mutations. The first is called the Paisa mutation (Presenilin-1 E280A), which is known to be present in a large family in Colombia. Previous research shows that people with the Paisa mutation are at a high risk of developing Alzheimer’s disease with symptoms beginning to show as early as their 40s.
The second genetic variant researchers examined in this study is on the APOE3 gene, called Christchurch (APOE3Ch).
The APOE gene contains directions needed to make a protein called apolipoprotein E. Different types of the APOE gene are known to contribute to the development of Alzheimer’s disease.
A study published in 2019 conducted by Mass General Brigham researchers showed a person with an extremely high genetic risk for Alzheimer’s disease and two copies of the Christchurch variant who did not develop cognitive impairment until her late 70s.
Another study in January 2024 found the Christchurch mutation may help protect the brain against clumps formed by excessive amounts of the protein tau, considered a hallmark of Alzheimer’s disease. Scientists analyzed genetic data from 1,077 descendants of the Colombian family with the Paisa mutation.
They identified 27 family members who carried both the Paisa mutation and one copy of the Christchurch variant. On average, these family members did not start to show signs of cognitive impairment until age 52, compared to family members who did not have the Christchurch variant and showed symptoms at age 47.
Researchers say that this illuminates a path forward for new drug targets in populations at the highest genetic risk for this devastating disease,” Sullivan explained. “It is a novel finding to see an APOE-related mechanism of increased protection rather than increased risk.
They think about 60-80% of Alzheimer’s disease cases are related to genetic variants. There will be no cure for Alzheimer’s disease without cracking the genetic code.
Learning details of various genetic variants is helpful in (the) implementation of care plans for the patients and their family members. Increasing access and education of the benefits of understanding genetic variants can allow us to help individuals and families with this disease with comprehensive care plans in a timely manner.
