If you live with or have lost a loved one to Alzheimer’s disease you may find yourself with an inbox filled with well-intentioned emails from family and friends, about the latest research on Alzheimer’s disease or the new cure that drug companies don’t want you to know about. A recent New York Times article hits a bit differently. Linde Jacobs is a woman in her 30s with two young daughters. Four weeks ago, she lost her mother to frontal temporal dementia (FTD) and the article begins with her waiting to hear her genetic test result, that is whether she has a mutant gene that will cause in her the same disease that afflicted her mother. She learns she does, meaning she will likely develop FTD, and that her daughters have 50-50 chance as well.
The article highlights the remarkable journey of a woman determined to do everything she can to stop her family’s devastating pattern of FTD. She presents her family’s story at scientific conferences, inspires scientists to study her family’s mutant gene, donates skin cells for research, and creates a nonprofit to unite others who carry the same mutant gene so they can eventually join clinical trials.
FTD causes a loss of brain cells, unique personality changes, and cognitive loss. Linde and some of her family members carry one of the mutant genes, called MAPT, that causes FTD. Scientists have discovered that being a carrier of MAPT means that there is a very high likelihood (nearly 99.9%) that a person will develop FTD, and a 50% chance of passing the mutated gene on to their children. MAPT is one of several mutant genes that can be passed on generation after generation in families with a history of young onset dementia.
In the Alzheimer’s disease community, there is also a rare young onset hereditary form of the disease caused by gene mutations. This is known as autosomal dominant or familial Alzheimer’s disease (FAD). Families with a mutation (genetic change or error) in the PSEN1, PSEN2, or APP genes often see multiple family members over generations develop Alzheimer’s disease at a young age, typically between their 40s and 50s. Like Linde’s story, these families wrestle with losing a parent at a young age, enduring frustrating diagnostic journeys, being caregivers for their parents while also taking care of young children, contemplating whether they would like to learn if they carry a mutant gene themselves, and dealing with possibility of passing the mutant gene onto their children, to name a few. Many of these FAD families are participating in clinical trials and helping to make groundbreaking discoveries about what causes the disease, what biomarkers can detect the disease sooner, and testing promising drugs (link to this: First Success Stories From Alzheimer’s Secondary Prevention Trial | ALZFORUM).
As the Founder of Youngtimers, a nonprofit dedicated to helping these families (link to www.youngtimers.org), I often receive questions from individuals who are worried that their family may carry one of these FAD mutant genes. Information about the autosomal dominant vs sporadic forms of Alzheimer’s disease is critical for these families.
The criteria for determining whether your family’s history of Alzheimer’s disease is autosomal dominant is the following:
- At least two family members in two successive generations (so a parent and their child) developed symptoms of Alzheimer’s disease before the age of 60.
Editor’s note: If a family member has undergone genetic counseling and testing and found to be a carrier of a mutation in the PSEN1, PSEN2, or APP genes, this is a confirmation that your family member has FAD and has a 50% chance of passing the mutation on to children.
If your family doesn’t fit these criteria, it is likely that your family is not at risk of carrying a mutant gene that causes FAD. Most people with dementia have or had a sporadic form of Alzheimer’s disease. While researchers are still trying to understand the genetics behind sporadic Alzheimer’s disease, the strongest genetic risk factor for this disease is APOE4. Unlike FAD, in which people who test positive for a genetic mutation have a near 99.9% chance of getting the disease, people who carry one or two copies of the APOE4 gene have a 2-15 fold increased risk of developing Alzheimer’s disease. It increases risk but does not cause the disease. Some people who have two copies of APOE4 live to 100 and never develop Alzheimer’s.
Lindsay Hohsfield, PhD, Associate Researcher
Losing a loved one to Alzheimer’s disease or any dementia is devastating. I lost my dad to Alzheimer’s disease when I was in my 20s and he was in his 50s. I carry that loss with me even 15 years after his passing. But it has also fueled incredible motivation and passion for finding a cure, for stepping into the lab each and every day, and for starting Youngtimers. We are here. Scientists who have lost loved ones, who care, who are inspired by your stories. We are not sitting on the sidelines, but doing the work so that in the future, no one has to lose a loved one to this disease again. So please don’t hesitate to send that email. Share your story with us. It’s what we’ve dedicated our careers and countless hours in dark rooms looking under microscopes to. We’re in this together.
