Research shows the pTau217 biomarker can identify risk for cognitive decline and amyloid buildup before changes appear on brain scans.
A new study published in Nature Communications indicates that a blood test for the biomarker plasma phosphorylated tau 217 (pTau217) can predict the progression of Alzheimer’s disease in cognitively healthy older adults.
Researchers from Mass General Brigham found that pTau217 levels can signal future amyloid positron emission tomography (PET) scan changes and cognitive decline years before clear abnormalities appear on imaging or symptoms emerge. The findings suggest that blood-based biomarkers may offer a simpler, earlier method for disease prediction.
“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,” says Hyun-Sik Yang, MD, a neurologist with Mass General Brigham Neuroscience Institute and lead author of the study, in a release. “But now we are seeing that pTau217 can be detected years earlier, well before clear abnormalities appear on amyloid PET scans.”
Predicting Amyloid Accumulation
The prospective cohort study followed 317 cognitively healthy older adults for an average of eight years. Participants, ranging in age from 50 to 90 years, underwent blood tests for pTau217, repeated amyloid and tau PET scans, and long-term cognitive testing.
The research team examined whether baseline and changing pTau217 levels predicted future amyloid buildup and tau accumulation, which is the abnormal buildup of misfolded proteins inside brain neurons. The data showed that higher levels of pTau217 predicted a faster buildup of Alzheimer’s pathology, even when initial brain scans appeared normal.
Increases in the biomarker frequently occurred before PET scans became positive for amyloid. Furthermore, participants with low pTau217 levels at the start of the study were unlikely to accumulate significant amyloid-beta over the follow-up period.
“What stood out in our study is that even when amyloid scans appear normal in the clinic, the pTau217 biomarker can identify individuals who later become amyloid-positive,” says Yang in a release. “It also shows that those with low pTau217 levels are likely to stay amyloid-negative for several years.”
Clinical and Research Implications
While researchers note it is too early to recommend routine pTau217 testing for all older adults, the study suggests the biomarker could serve as a scalable screening tool for clinical trials focused on Alzheimer’s prevention.
Last year, the Food and Drug Administration cleared the first blood test for Alzheimer’s disease. These diagnostic advancements provide less invasive and more affordable alternatives to lumbar punctures and PET scans.
“As the field is evolving quickly, we’re excited to see discoveries on the research side being rapidly translated to clinical application,” says Jasmeer Chhatwal, MD, PhD, a neurologist with Mass General Brigham Neuroscience Institute and co-senior author, in a release. “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.”
ID 434316450 © Dahlia Begum | Dreamstime.com
