A woman in Colombia was destined to develop Alzheimer’s disease in middle age due to a genetic mutation. But she never did. In fact, she made it into her 70s showing no signs of dementia.
A few years back, the woman partook in a study at the University of Antioquia in Colombia that looked at 6,000 people that she was distantly related to. About a fifth of these participants, including the woman in question, had a genetic predisposition to Alzheimer’s. She carried a mutation in the gene responsible for a protein called presenilin 1, giving her a greater than 99 percent risk of developing dementia and cognitive issues in her 40s or 50s. But she remained in good cognitive health.
To satisfy the curiosity of baffled scientists, she headed to Boston in 2016 to have her brain, blood, and genome examined. Scans of her brain revealed high levels of amyloid protein, a hallmark of Alzheimer’s disease. However, she was symptom-free, suggesting something mysterious was protecting her from its effects.
Next, the researchers sequenced her genome, finding that she had a very rare mutation of a gene called APOE. This gene has previously been implicated in Alzheimer’s – one variation can increase risk, another can decrease it, while the most common type has no effect. However, the woman had two copies of another variant, known as Christchurch, which was discovered in 1987 in Christchurch, New Zealand. The findings are reported in Nature Medicine.
The researchers think that the Christchurch mutation might prevent the APOE protein from binding with certain sugars, a process implicated in the build-up of amyloid proteins and tau proteins, another Alzheimer’s hallmark, in the brain. Therefore, a drug that inhibits this process could stave off the disease, although such a drug likely would not be available soon.
Early-onset Alzheimer’s affects a small minority of people and only about 5 percent of Alzheimer’s patients are diagnosed with it. The condition can have substantial impacts on a person’s life as it tends to develop during your 40s or 50s, decades before Alzheimer’s symptoms usually start to set in. Alzheimer’s is a progressive disease, meaning that symptoms like memory loss, confusion, and delusions get worse over time. There’s currently no cure, so gaining a better understanding of what causes the condition is key.
“Sometimes close analysis of a single case can lead to a discovery that could have broad implications for the field,” said National Institute of Aging Director Richard J. Hodes in a statement. “We are encouraged that as part of our wide array of studies, this research in the unique genetic makeup of an exceptional individual can reveal helpful information.”