'Alzheimer’s clock': Highly accurate blood test can predict what age symptoms may start, study finds

ST. LOUIS - Scientists say they’ve developed a highly accurate, single blood test that can predict within three to four years when a person is likely to start experiencing symptoms of Alzheimer’s disease (AD).

Researchers at the Washington University School of Medicine in St. Louis helped develop the new tool, as part of an effort launched by the public-private partnership known as Foundation for the National Institutes of Health Biomarkers Consortium.

What they're saying:

"Eventually, the goal is to be able to tell individual patients when they are likely to develop symptoms, which will help them and their doctors to develop a plan to prevent or slow symptoms," said associate professor in the WashU Medicine Department of Neurology Dr. Suzanne E. Schindler in a news release.

'Alzheimer’s clock'

Schindler is senior author of a new study that demonstrated how the blood test could provide an "Alzheimer’s clock" to predict when symptoms would appear within a margin of error of three to four years.

"We aimed to use measurements from a single plasma sample to estimate not only the probability of a cognitively unimpaired individual with positive AD biomarkers developing AD symptoms but also when they would be likely to develop symptoms," researchers wrote in Nature Medicine where the study was published.

Dig deeper:

Alzheimer’s patients have an abnormal buildup of amyloid plaques and tau tangles in the brain. These proteins start accumulating well before symptoms appear. 

Researchers honed in on what’s known as plasma phosphorylated tau 217, or p-tau217, which has shown to strongly correlate with amyloid and tau accumulation in the brain. Thus, elevated levels of p-tau217 have served as early blood-based markers to help doctors determine Alzheimer’s in patients with cognitive deterioration.

"The models that Schindler and her colleagues developed use a protein called p-tau217 in an individual’s plasma, the liquid part of the blood, to estimate the age when they will begin experiencing symptoms of the neurodegenerative disease," researchers detailed in a WashU Medicine news release.

Researchers said to determine the trajectory of when elevated p-tau217 levels will show up in symptoms, they analyzed data from 603 older adult participants in two independent long-running Alzheimer’s research initiatives.

"Interestingly, once amyloid plaques and neurofibrillary tangles start to accumulate, the burden of pathology follows a remarkably consistent trajectory across individuals," researchers wrote in Nature Medicine. 

That trajectory, researchers explained, could allow experts to create a clock model signaling when to expect the onset of Alzheimer’s symptoms. 

Like ‘tree rings’

Scientists described amyloid and tau levels as revealing markers similar to tree rings.

"If we know how many rings a tree has, we know how many years old it is," said WashU Medicine neurologist and study co-author Kellen K. Petersen said. "It turns out that amyloid and tau also accumulate in a consistent pattern and the age they become positive strongly predicts when someone is going to develop Alzheimer’s symptoms. We found this is also true of plasma p-tau217, which reflects both amyloid and tau levels."

Other similar blood test predictors

Other recent studies have honed in on the use of blood tests to forecast the risk of a person’s decline in memory and cognitive function. 

A new study by researchers with the University of California San Diego revealed a blood-based biomarker identifying elevated levels of p-tau217 can predict a woman’s risk of developing dementia as far out as 25 years before symptoms appear. 

UCSD researchers found a strong correlation between high levels of  p-tau217 and future dementia among older women who showed no symptoms of cognitive impairment at the start of the study.

That study was based on information from 2,766 cognitively healthy women ages 65 to 79. The subjects were participants in a large national study known as the Women’s Health Initiative Memory Study, which began following participants from the late 1990s over a period of up to 25 years. 

Researchers collected blood samples at the start of the study as baseline. They then analyzed the samples to measure p-tau217.

The findings showed that those with the highest level of the protein had the greatest likelihood of developing dementia over the long term.

"As levels of this biomarker increased, so did dementia risk," UCSD researchers said.

They stressed that the findings are critical in accelerating research on risk factors for dementia and evaluating ways to reduce that risk.

"That kind of long lead time opens the door to earlier prevention strategies and more targeted monitoring, rather than waiting until memory problems are already affecting daily life," said lead author UCSD Associate Professor of Public Health, Human Longevity Science, and Medicine Aladdin H. Shadyab. "Ultimately, the goal is not just prediction but using that knowledge to delay or prevent dementia altogether."

Big picture view:

Alzheimer's is the most common form of dementia

Figures show more than 7 million Americans live with the disease. The condition progressively destroys nerve cells, leading to memory failure, personality changes, and impairs the ability to perform daily activities.

"The greatest known risk factor is increasing age, and the majority of people with Alzheimer's are 65 and older, according to the Alzheimer’s Association. 

Currently, there is no cure. 

"But predictive models could help efforts to develop treatments that prevent or slow the onset of Alzheimer’s symptoms," WashU Medicine neurologists said.

Previous research on predicting the disease includes using Positron Emission Tomography (PET) scans to identify the presence and accumulation of amyloid plaques and tau tangles.

Another option is conducting spinal fluid tests, a highly invasive process.

Diagnosing Alzheimer’s through these avenues is costly and with accessibility barriers.

Benefits of blood test 

"Our work shows the feasibility of using blood tests, which are substantially cheaper and more accessible than brain imaging scans or spinal fluid tests, for predicting the onset of Alzheimer’s symptoms," said Schindler.

The expert also pointed to the fact that the blood test would also lead to clinical trials of potentially preventive treatments within a shorter time period.

"In the near term, these models will accelerate our research and clinical trials," Schindler explained. 

While the models were able to predict symptoms' appearance within a margin of three to four years, researchers said their findings also revealed that older people had a shorter time from when elevated p-tau217 was first detected to the onset of symptoms, relative to the younger participants.

Scientists said that the findings suggest that younger patients' brains may be more resilient to cognitive decline and that older people may develop symptoms at lower levels of amyloid and tau accumulations. 

"For example, if a person had elevated p-tau217 in their plasma at age 60, they developed symptoms 20 years later," experts explained. "If p-tau217 wasn’t elevated until age 80, they developed symptoms only 11 years later."

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Scientists also developed a web-based app to help other researchers use the clock models to predict Alzheimer’s onset and to help advance clinical trials for treatments of the disease. 

"These clock models could make clinical trials more efficient by identifying individuals who are likely to develop symptoms within a certain period of time," Petersen said.

Researchers did note that these blood tests were currently not recommended for those who don’t exhibit cognitive impairment, outside of clinical research settings.

And they encouraged expanded research on additional blood biomarkers for Alzheimer's.

"With further refinement," Petersen said, "these methodologies have the potential to predict symptom onset accurately enough that we could use it in individual clinical care."

This story was reported from Oakland, Calif.