A blood test may predict if apparently healthy older adults are likely to develop Alzheimer’s symptoms in the next five or 10 years, researchers reported Wednesday. The findings could offer a potential tool to speed drug development by helping to identify and enroll high-risk individuals into studies of possible Alzheimer's treatments or preventive strategies.

Large clinical trials are already testing if certain drugs could prevent or delay the disease, and if successful, doctors will need an accessible method to identify candidates.

The scientists behind the new study emphasize that it is too early for healthy individuals to seek out the p-tau217 test. Currently, it is used to help diagnose whether people experiencing cognitive problems have Alzheimer's or another disorder.

"Wait and get tested when you can potentially do something about it," said Dr. Reisa Sperling of the Mass General Brigham Neuroscience Institute, the study’s senior author. "At this point it wouldn’t change what I would tell someone to do. I’d still tell them to eat well, sleep well, exercise a lot and stay engaged."

Risk Assessment

The new findings indicated that symptom-free older adults with very high levels of p-tau217 had a 38% risk of developing cognitive impairment over five years, a risk that grew to 78% by 10 years. The research was published in JAMA and presented at the Alzheimer’s Association International Conference in London.

Alzheimer's disease is characterized by brain-clogging amyloid plaques and neuron-killing tau tangles. The p-tau217 test measures a form of tau that correlates with the amount of plaque buildup in the brain and provides an indication of tangles, Sperling explained.

The Mass General Brigham team analyzed data from 2,684 older adults who were healthy at the start of long-running Alzheimer's studies. Participants received the p-tau217 blood test at enrollment and underwent yearly cognitive checkups. Between the earliest enrollment in 2004 and last year, approximately 478 participants developed cognitive impairment.

Conversely, study participants with very low p-tau217 levels showed a low risk of developing cognitive impairment over the five- to 10-year period.

Navigating Uncertainty

A challenge in predicting Alzheimer's is that many individuals with high levels of amyloid plaques do not develop dementia. A leading theory suggests that amyloid buildup eventually triggers abnormal tau to form tangles, leading to symptoms.

Sperling noted that the blood test data provides new insights. While varying intermediate levels of p-tau217 signaled progressive risk, only the highest level appeared to correlate with evidence of a critical tipping point.

"This is a gradual process where amyloid and tau build up in the brain and this blood-based biomarker is telling you how far you are in that process," she said.

Scientists not involved in the study offered praise alongside notes of caution. One concern is that only a small fraction of participants were tracked for a full decade, making the 10-year risk estimate less certain than the five-year estimate. Additionally, other factors could influence predictions, such as the risk of dying from other causes or the presence of heart-related problems that can lead to vascular dementia rather than Alzheimer's, according to Drs. Suzanne Schindler of Washington University in St. Louis and David Wolk of the University of Pennsylvania in a JAMA commentary.

"The blood tests are not yet precise enough to guide individualized prognosis," wrote Schindler and Wolk. However, they added that the new work has "provided a crucial piece of the puzzle."

Jessica Langbaum of the Banner Alzheimer's Institute in Phoenix noted that some individuals are already inquiring about the test due to family history, a step she currently discourages.

"These findings are quite strong," Langbaum said, adding that a predictive blood test would be "really important" but contingent on ongoing studies identifying a drug that could benefit individuals before symptoms manifest.