In the town of Medellin, Colombia, an extended family of more than 6,000 have an extremely high risk of developing Alzheimer’s disease in their mid 40’s due to a rare genetic mutation in the presenilin 1 (PSEN1) gene. So why did one woman with this mutation show no signs of memory loss until her 70’s? It’s a question scientists are now pursuing to see if her experience can help others inflicted by the memory stealing disease.
Many members of the family are currently participating in a groundbreaking clinical trial to test a medication to prevent them from developing the disease that takes their family members by the age of 60. The study is being conducted by physicians and scientists in Colombia and the United States.
“We identified this woman about three years ago,” explained Yakeel T. Quiroz, Ph.D., assistant professor at Harvard Medical School and Massachusetts General Hospital and a clinical scientist in the Colombian study. “She did not begin to develop memory and thinking problems until three decades after we expected. So, we brought her and her family to Boston to try to determine what protected her from Alzheimer’s disease.”
The results were startling. The woman carries the PSEN1 genetic mutation shared by this family that destines so many of its members to lose their ability to think and function in middle age. Brain imaging showed significant amounts of amyloid in the brain. Amyloid is a plaque found in the brains of most people with Alzheimer’s and the focus of many current Alzheimer’s prevention studies.
In this family, amyloid build up is one of the first brain changes, followed by brain shrinkage and the accumulation of a protein called tau. The woman showed very limited atrophy or tau in her brain. She had normal memory and thinking until her 70’s when she began to develop age related memory decline.
“Our significant finding is a different mutation known as Christchurch on the APOE gene, which is associated with risk for Alzheimer’s disease,” said Dr. Quiroz. “This Christchurch mutation appears to block the binding of the gene to certain sugars. For this woman it seemed to have blocked the development of tau pathology and brain atrophy and then slowed down the progression of disease.” Thus, while the woman should have developed Alzheimer’s in her mid-40s, she did not experience memory and thinking problems for three more decades.
Scientists believe this new discovery may change their understanding of Alzheimer’s disease and spur new approaches for treatment. The next step for the scientific team is to test the performance of the Christchurch mutation in the laboratory. They are also searching for other family members who developed memory problems at later stages of life to see if they have been protected by similar genetic factors.
“This new finding gives hope to people who already have brain changes and are beginning to experience memory loss and Alzheimer’s symptoms,” said Dr. Quiroz. “We are very optimistic this could lead to the creation of a treatment that mimics the Christchurch mutation and blocks the development of Alzheimer’s after the brain has begun to change.”
Treatments related to this genetic mutation are several years away, but there are many other clinical trials currently in progress. If you or a family member are interested in participating in a study, check out the current listings on the Alzheimer’s Prevention Registry website.