Summary: For years, amyloid PET scans were considered the earliest reliable sign of Alzheimer’s disease, identifying brain plaque buildup a decade or two before symptoms. A new study now identifies an even earlier warning: a blood marker called pTau217 (phosphorylated tau 217) that can predict future amyloid accumulation and cognitive decline long before PET scans show abnormalities.
Researchers report that a simple plasma pTau217 blood test can forecast which cognitively healthy older adults will later develop amyloid positivity and cognitive decline, even when their initial brain imaging appears normal. This advance could shift screening from costly, invasive imaging toward affordable, scalable blood tests integrated into routine care and clinical trial recruitment.
Key Facts
- Scalable screening: pTau217 testing uses a standard blood draw, avoiding the cost and radiation exposure of PET scans and the invasiveness of lumbar punctures.
- Earlier detection: Elevated pTau217 levels often precede PET-detectable amyloid accumulation, revealing Alzheimer’s-related changes years before standard scans.
- Robust dataset: Results come from the Harvard Aging Brain Study (HABS), a prospective cohort with nearly a decade of longitudinal clinical, imaging, and blood biomarker data.
- Clinical use today: While not yet recommended for routine screening of healthy seniors, pTau217 is already helping to streamline enrollment for Alzheimer’s prevention trials.
- Regulatory context: The FDA cleared the first Alzheimer’s blood test in 2025; this study strengthens evidence that blood biomarkers can predict long-term disease trajectories.
Source: Mass General
Overview of the new study
Investigators at Mass General Brigham analyzed plasma pTau217 levels in cognitively unimpaired older adults and tracked changes in amyloid and tau PET imaging and cognitive performance over time. The study shows that higher baseline pTau217 values—and rising pTau217 over time—are associated with faster accumulation of Alzheimer’s pathology on PET and greater subsequent cognitive decline.
Published in Nature Communications, the study challenges the long-held view that amyloid PET positivity is the earliest detectable sign of Alzheimer’s disease. “We used to think PET scans were the first indicator, revealing amyloid decades before symptoms,” said lead author Hyun-Sik Yang, MD. “Our data show pTau217 can be measurable even earlier, offering a preclinical signal that precedes clear PET abnormalities.”
This prospective analysis followed 317 cognitively healthy participants from HABS for an average of eight years. Participants aged roughly 50 to 90 underwent repeated plasma pTau217 testing, serial amyloid and tau PET imaging, and long-term cognitive assessment. The investigators examined whether baseline and longitudinal pTau217 predicted later amyloid and tau PET changes and cognitive outcomes.
Key findings include:
- Higher baseline pTau217 predicted more rapid amyloid and tau accumulation on PET imaging and greater cognitive decline.
- In many individuals who were amyloid PET-negative at baseline, higher pTau217 anticipated later increases in amyloid and tau PET signals.
- Participants with very low pTau217 at baseline rarely developed significant amyloid pathology over many years, suggesting a low near-term risk.
Co-senior author Jasmeer Chhatwal, MD, PhD, noted the potential impact on prevention research: “By forecasting who is likely to turn amyloid-positive, we can move the timeline for Alzheimer’s prediction earlier and identify candidates for early interventions and clinical trials.”
Although pTau217 testing shows strong predictive promise, the authors caution that it is not yet recommended as a widespread screening test for all older adults. For now, its most immediate use is to enhance trial enrollment and target preventive strategies to those at higher risk. Over time, blood-based biomarkers like pTau217 could become part of routine health maintenance for people over 50, offering a more affordable route to early detection than PET imaging.
Authorship and disclosures
The study was led by Hyun-Sik Yang and Jasmeer P. Chhatwal, with contributing authors from Mass General Brigham including Juliana A. U. Anzai, Wai-Ying Wendy Yau, Brian C. Healy, Andrea M. Román Viera, Courtney Maa, Dylan Kirn, Michael J. Properzi, Jean-Pierre Bellier, Aaron P. Schultz, Michelle E. Farrell, Heidi I. L. Jacobs, Rachel F. Buckley, Kathryn V. Papp, Gad A. Marshall, Rebecca E. Amariglio, Dorene M. Rentz, Lei Liu, Dennis J. Selkoe, Keith A. Johnson, and Reisa A. Sperling, among others. Additional authors include Philip B. Verghese and Joel B. Braunstein.
Disclosures: Philip B. Verghese and Joel B. Braunstein are full-time employees of C2N Diagnostics LLC. Other authors report no directly relevant conflicts of interest.
Funding: Support came from grants K23 AG062750, K23 AG084868, P01 AG036694 (Harvard Aging Brain Study), R01 AG071865 from the National Institute on Aging, and a philanthropic gift from the Shelby Cullom Davis Charitable Fund.
Key Questions Answered
A: A normal PET scan reflects the brain’s status today. The pTau217 blood test provides information about early molecular changes that often occur before amyloid plaques are visible on PET, so it can indicate future risk rather than current disease alone.
A: The FDA cleared the first Alzheimer’s blood test in 2025 and similar assays are increasingly used in clinical settings, mainly for people with symptoms. This study supports extending blood-based testing to identify at-risk but cognitively unimpaired individuals, which could expand availability for routine screening in the coming years.
A: Elevated pTau217 indicates higher risk of future amyloid positivity and cognitive decline, but it is not a definitive diagnosis. Its greatest utility is as an early warning that enables monitoring, lifestyle changes, and potential enrollment in prevention trials.
Editorial Notes
- This article was edited by a Neuroscience News editor.
- The journal article was reviewed in full for accuracy.
- Additional context was provided by editorial staff.
About this Alzheimer’s disease research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: Image credited to Neuroscience News
Original Research: Open access. Title: “Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults” by Hyun-Sik Yang et al., published in Nature Communications. DOI: 10.1038/s41467-026-71269-3.
Abstract (summary)
Plasma pTau217 is a strong biomarker for Alzheimer’s pathology. Using mass spectrometry-based measures of pTau217 expressed as a percentage relative to non-phosphorylated tau, the study links higher baseline pTau217 with faster amyloid and tau accumulation on PET and greater cognitive decline. Among individuals who were amyloid PET-negative at baseline, higher pTau217 predicted later increases in amyloid and tau signals. Very low pTau217 was associated with minimal risk of Alzheimer’s pathology accumulation and cognitive decline over the follow-up period.