Columbia University researchers have identified a way to help predict when people with a high risk of developing Alzheimer's are likely to develop their first symptoms, a finding that could help physicians decide when to prescribe preventive treatments that are currently in development.
The study, published Sept. 9 in The Lancet Neurology, analyzed data from roughly 8,500 participants from different ethnic backgrounds and found that combining two Alzheimer's tests-a blood test that measures a biomarker known as p-tau217 and a genetic test that looks for a high-risk variant of the APOE gene-can predict symptom onset in people who are not currently experiencing symptoms.
Once p-tau217 tau levels become elevated, the study found, people with one or more copies of the high-risk APOE4 gene are likely to develop symptoms in 3 or 4 years, while people with other APOE variants are likely to develop symptoms in 5 to 6 years.
"The combination of the tests really makes a difference in predictive power. And the projections are the same for everyone regardless of their background," says Richard Mayeux, chair of the Department of Neurology at Columbia University Vagelos College of Physicians and Surgeons and neurologist-in-chief at NewYork-Presbyterian/Columbia University Irving Medical Center.
"What this will allow us to do is make better predictions about the onset of symptoms in people at risk, and when preventative drugs become available, prescribe those at the right time."
In the last few years, new blood tests that measure ptau-217-a biomarker for amyloid and tau pathology in the brain-have changed the landscape of Alzheimer's diagnosis and neurologists now commonly use the test to confirm or rule out Alzheimer's disease in older adults with memory loss or cognitive decline.
High levels of ptau can also be found in people who have yet to show symptoms, raising the possibility of using ptau as an early indicator of Alzheimer's, but predictions based on ptau alone are not robust enough for such use.
Mayeux's team asked if combining ptau with tests for another risk factor-the APOE4 gene-would improve predictions of symptom onset. APOE4 is the strongest genetic risk factor for Alzheimer's disease, and about one in five people at least one copy of the gene.
Though their findings could conceivably help people plan for the future, "I don't recommend that people get these tests right now if they're asymptomatic," Mayeux says. "What would you do with that information?" People without symptoms are not eligible to receive monoclonal antibody drugs approved for Alzheimer's.
The situation could change rapidly in the future. A study currently underway will determine if the antibody drugs can slow disease progression when given to asymptomatic people with elevated p-tau217 levels.
Many other drugs that may slow the disease are in development, and the new findings will be important when clinical trials to test these drugs begin.
"If you have a drug that could prevent disease, what would be the optimal time to give it to people? Our data is telling us, for people at high risk with APOE4 genes, the best time is when their ptau levels elevate, about three years before symptoms emerge," Mayeux says.
