- A study suggests that a blood test measuring the biomarker pTau217 can detect early signs of Alzheimer’s disease years before symptoms or signs appear on brain scans.
- Higher pTau217 levels in cognitively healthy adults were linked to faster buildup of amyloid and tau proteins, as well as future cognitive decline.
- Changes in pTau217 often occurred before positive scans, suggesting it may be a more sensitive early detection tool.
- Low pTau217 levels were associated with a lower likelihood of developing significant Alzheimer’s-related brain changes over many years.
Estimates suggest that more than 7 million American adults are living with Alzheimer’s disease. Receiving a timely diagnosis can provide many benefits, such as helping to reduce cognitive and functional decline and allowing an individual to prioritize their health.
At present, diagnosis typically involves a combination of medical history, cognitive tests, neurological exams, and brain imaging. However, growing evidence is highlighting the possible role of certain proteins in diagnosing Alzheimer’s disease.
The accumulation of these proteins can begin years before clinical symptoms and may serve as measurable, specific biomarkers of underlying neuropathology. As such, they may allow for earlier and more accurate diagnosis than current methods.
Traditionally, clinicians have used brain imaging techniques, such as amyloid PET scans, to help detect early changes linked to Alzheimer’s disease. These scans can be effective at identifying early, even preclinical, signs of Alzheimer’s disease by detecting proteins in the brain, often before significant cognitive decline begins.
However, measuring for blood-based biomarkers may offer even earlier detection.
“We used to think that PET scan detection was the earliest sign of Alzheimer’s disease progression, revealing amyloid accumulation in the brain 10 to 20 years before symptoms appear,” said lead author Hyun-Sik Yang, MD, in a press release. “But now we are seeing that pTau217 can be detected years earlier, well before clear abnormalities appear on amyloid PET scans.”
The results build on recent momentum in the field, including the decision by the Food and Drug Administration to clear the first blood test for Alzheimer’s disease in 2025.
“For researchers, our results suggest that plasma pTau217 levels might be one of the earliest predictors of future Alzheimer’s disease progression and could be used to screen clinical study participants to identify individuals at risk of developing Alzheimer’s disease pathology and symptoms,” Yang told Medical News Today.
“For clinicians, I would not recommend using plasma pTau217 to screen cognitively unimpaired older adults,” he added. “Whether intervening in [Alzheimer’s] pathology at this early stage is beneficial remains unknown, so the clinical benefit of early screening strategies is unclear.”
“However, this study adds further evidence that plasma pTau217 performs robustly in detecting [Alzheimer’s] pathology, and, as many other studies suggest, plasma biomarker testing is an option to consider when evaluating patients with cognitive impairment.”
— Hyun-Sik Yang, MD
Led by a team from Mass General Brigham, the research followed 317 cognitively healthy adults enrolled in the Harvard Aging Brain Study for an average of 8 years.
Participants ranged in age from 50 to 90 and underwent regular blood testing, brain imaging, and cognitive assessments.
The team examined whether initial levels and changes over time of pTau217 could help predict amyloid buildup in the brain, tau protein accumulation, and cognitive decline.
They found that individuals with higher pTau217 levels typically experienced faster progression of Alzheimer’s-related brain changes.
Notably, increases in pTau217 often occurred before amyloid PET scans turned positive, suggesting the biomarker could detect disease activity at an earlier stage.
“We were surprised to see it predict future amyloid-β accumulation even in those with low amyloid-β PET signals, i.e., in the “negative” range, because we had thought that brain amyloid-β accumulation is an initial event and that plasma pTau217 elevation would follow it,” Yang explained to MNT.
“We suspect our observation was driven by the relative sensitivity of the tests (i.e., plasma pTau217 might be more sensitive than amyloid-β PET in very early stages) rather than pTau217 driving amyloid-β accumulation. Nonetheless, our results have significant implications for clinical study design and biomarker panel selection,” he continued.
The findings also show that those with low baseline pTau217 levels were less likely to develop significant amyloid buildup over many years.
“Personally, I think this finding may have the greatest practical utility for clinical study design and, once effective [Alzheimer’s] prevention strategies become available, for [Alzheimer’s] risk stratification in the clinic.”
— Hyun-Sik Yang, MD
“We observed that cognitive-unimpaired older adults with very low baseline pTau217 rarely became amyloid-positive (elevated amyloid-β on PET) during the PET scan follow-up period, which was on average about 6 years,” Yang said to MNT.
“This means that those with very low pTau217 levels are at a low risk of [Alzheimer’s] progression, and [Alzheimer’s] prevention trials might want to consider excluding this subgroup of people to optimally power their studies,” he added.
Although the findings could have important implications for clinical trials and future screening strategies, the researchers caution that it is too soon to recommend routine pTau217 testing for the general population.
“There are already 2 FDA-approved pTau217 blood tests in clinical use. As more data accumulate, blood tests—especially pTau217—appear to be as good as, or even better than, cerebrospinal fluid testing and show excellent concordance with amyloid-β PET,” Yang told MNT.
“Given their greater accessibility, blood-based biomarkers are poised to replace more invasive or expensive tests in the near future, at least for diagnostic purposes,” he said.
“Nonetheless, given the prolonged preclinical phase of Alzheimer’s disease, clinical judgment cannot be fully replaced by biomarker testing, because elevated pTau217 or Aβ signals do not necessarily mean that [Alzheimer’s] pathology is the main driver of the patient’s symptoms; this part still requires clinicians’ judgment.”
— Hyun-Sik Yang, MD
“I would also emphasize that plasma pTau217 measurements are not currently recommended for screening in cognitively unimpaired individuals. The clinical benefits of broader screening remain unclear, and pTau217 screening is appropriate only in research settings,” Yang concluded.
Co-senior author Jasmeer Chhatwal, MD, PhD, notes that the goal is to identify individuals at risk earlier, when preventive treatments may be more effective.
“By anticipating who’s going to turn amyloid-positive in the future, we are trying to push back the clock to enable earlier Alzheimer’s disease prediction,” Chhatwal said in a press release.
As research continues, blood-based biomarkers like pTau217 could become part of routine health checks, offering a more accessible and affordable alternative to current diagnostic methods.
These tests could play a central role in shifting Alzheimer’s care toward earlier diagnosis, targeted prevention, and more personalized treatment strategies.
