Summary: For years, amyloid PET scans were considered the earliest reliable marker of Alzheimer’s disease, revealing brain amyloid plaques a decade or two before symptoms. A new study, however, shows that a blood test measuring plasma phosphorylated tau 217 (pTau217) can detect Alzheimer’s pathology even earlier — identifying people at risk before amyloid PET scans become abnormal.
Researchers report that a simple blood draw for pTau217 predicted later amyloid accumulation on PET scans and subsequent cognitive decline in cognitively healthy older adults. If adopted widely, this approach could shift screening away from costly PET imaging and invasive lumbar punctures toward an affordable, scalable blood test used in routine care and prevention trials.
Key Facts
- Scalable screening: A pTau217 plasma test requires only a blood draw, unlike amyloid PET scans, which are expensive and involve radiation, or lumbar punctures, which are invasive.
- Earlier detection: Elevated pTau217 often appears before amyloid PET scans become positive, allowing detection of Alzheimer’s-related changes at an earlier molecular stage.
- Robust cohort data: Findings come from the Harvard Aging Brain Study (HABS), a prospective cohort with high-quality longitudinal data spanning nearly a decade.
- Clinical use and trials: While routine clinical use for healthy older adults is not yet recommended, pTau217 testing is already being used to screen and streamline Alzheimer’s prevention trials.
- Regulatory context: The U.S. Food and Drug Administration cleared the first Alzheimer’s blood test in 2025; this study strengthens evidence that blood biomarkers can predict long-term disease progression.
Source: Mass General
Overview of the study
Investigators at Mass General Brigham report that plasma pTau217 predicts future changes in amyloid PET, tau PET, and cognition in older adults who were cognitively unimpaired at baseline. The study suggests pTau217 can serve as an early indicator of Alzheimer’s disease risk, potentially years before traditional imaging shows clear abnormalities.
The full results are published in Nature Communications. Lead author Hyun‑Sik Yang, MD, and colleagues observed that pTau217 elevations frequently preceded amyloid PET positivity, and higher baseline pTau217 predicted faster accumulation of both amyloid and tau on PET and greater cognitive decline over time.
This prospective analysis followed 317 cognitively healthy participants from HABS for an average of eight years. Participants, aged 50 to 90, underwent repeated plasma pTau217 testing, serial amyloid and tau PET imaging, and long-term cognitive assessments. The investigators evaluated whether baseline pTau217 and changes over time forecasted later amyloid and tau buildup and declines in cognitive performance.
Key findings included that higher baseline pTau217 was associated with faster rates of amyloid and tau accumulation on PET scans, which in turn were linked to steeper cognitive decline. Among participants whose amyloid PET scans were negative at the start, elevated pTau217 predicted subsequent increases in amyloid and tau PET signal. Conversely, very low pTau217 at baseline identified individuals with minimal risk of accumulating Alzheimer’s pathology over several years.
“Previously, amyloid PET was thought to be the earliest measurable marker of Alzheimer’s disease,” said Yang. “Our data show that plasma pTau217 can be detected earlier in many people, identifying those who will later turn amyloid-positive and helping to stratify risk long before scans become abnormal.”
Co‑senior author Jasmeer Chhatwal, MD, PhD, emphasized the translational potential: the blood biomarker could be used to screen large numbers of asymptomatic adults for enrollment in prevention trials or, in the future, for routine risk assessment as part of preventive health care.
Authorship and disclosures
In addition to Hyun‑Sik Yang and Jasmeer Chhatwal, Mass General Brigham authors include 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. 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: This research was supported by grants K23 AG062750, K23 AG084868, P01 AG036694 (Harvard Aging Brain Study), and R01 AG071865 from the National Institute on Aging, and by a philanthropic gift from the Shelby Cullom Davis Charitable Fund.
Frequently asked questions
A: A normal PET scan shows the current state of brain amyloid. A pTau217 blood test indicates early molecular changes that often precede visible amyloid plaques, offering insight into what may develop next and identifying risk earlier than imaging alone.
A: The FDA cleared the first Alzheimer’s blood test in 2025, and tests measuring pTau217 are increasingly used in specialty centers and clinical trials. Widespread routine screening for asymptomatic people is not yet standard, but this evidence supports broader clinical adoption in the near future.
A: Elevated pTau217 signals a higher risk of developing amyloid pathology and cognitive decline, but it is not a definitive diagnosis. The value of early detection lies in targeting prevention strategies, lifestyle changes, and potential therapies earlier in the disease course.
Editorial notes
- This article was edited by a Neuroscience News editor.
- The journal paper was reviewed in full by the editorial team.
- Additional context was added by staff to explain clinical implications.
About this Alzheimer’s research news
Author: Brandon Chase
Source: Mass General
Contact: Brandon Chase – Mass General
Image: The image is credited to Neuroscience News
Original research (open access):
“Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults” by Hyun‑Sik Yang et al., Nature Communications.
DOI: 10.1038/s41467-026-71269-3
Abstract (condensed)
Plasma phosphorylated tau 217 and longitudinal trajectories of Aβ, tau, and cognition in cognitively unimpaired older adults
Plasma pTau217 is a strong biomarker of Alzheimer’s disease pathology. Using mass spectrometry–based measures of pTau217 relative to non‑phosphorylated tau, the study evaluated associations with longitudinal amyloid and tau PET and cognitive outcomes in a well‑characterized cohort of cognitively unimpaired older adults. Higher baseline pTau217% correlated with faster amyloid and tau accumulation on PET and with greater subsequent cognitive decline. Among participants who were amyloid PET‑negative at baseline, higher pTau217 predicted later increases in amyloid and tau PET signals. Very low pTau217 levels were associated with minimal risk of accumulating AD pathology and cognitive decline over the follow-up period.