Blood test for pTau217 can predict Alzheimer’s disease progression years before PET brain scan sees changes

Plasma pTau217 has predicted amyloid accumulation and cognitive decline in healthy older adults, which has offered a potential route to earlier and less invasive detection of Alzheimer’s disease

A blood-based biomarker has predicted the earliest stages of Alzheimer’s disease progression in cognitively healthy older adults, according to a study by investigators at Mass General Brigham, Boston, USA. The research has shown that plasma phosphorylated tau 217 (pTau217) can anticipate amyloid pathology and cognitive decline well before conventional imaging detects abnormalities, which has raised the prospect of earlier and less invasive disease detection. 

The study centred on pTau217 a circulating biomarker linked to tau pathology in Alzheimer’s disease. Historically, amyloid positron emission tomography (PET) has served as the earliest reliable indicator of disease progression, with detection of amyloid-beta accumulation in the brain estimated to occur between 10 and 20 years before clinical symptoms. However, the present work has indicated that pTau217 becomes detectable even earlier in the disease trajectory.

“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 Dr. Hyun-Sik Yang, lead author and neurologist at the Mass General Brigham Neuroscience Institute and associate member of the Broad Institute of MIT and Harvard.

“But now we are seeing that pTau217 can be detected years earlier, well before clear abnormalities appear on amyloid PET scans,” he said.

The findings have built on recent regulatory progress in blood-based diagnostics. The U.S. Food and Drug Administration has cleared the first blood test for Alzheimer’s disease, which has opened a pathway towards more accessible and less invasive screening compared with lumbar puncture or PET imaging. The present study has added prospective evidence that such assays may hold predictive value rather than merely diagnostic utility.

Investigators conducted a longitudinal cohort analysis involving 317 cognitively unimpaired older adults enrolled in the Harvard Aging Brain Study. Participants, aged between 50 and 90 years, underwent serial blood sampling for pTau217, repeated amyloid and tau PET imaging, and extended neuropsychological assessment across an average follow-up period of eight years. The researchers examined both baseline concentrations and longitudinal changes in pTau217 to determine whether these measures could forecast subsequent amyloid deposition, tau accumulation within neurons, and cognitive decline.

The results have demonstrated that elevated pTau217 levels at baseline predicted a more rapid accumulation of Alzheimer’s-related pathology, even in individuals whose initial PET scans appeared normal. In many cases, increases in pTau217 preceded the transition to amyloid-positive PET status, which has underscored the biomarker’s sensitivity to preclinical disease processes. Conversely, participants who presented with low baseline pTau217 levels remained highly unlikely to develop substantial amyloid-beta deposition during extended follow-up.

“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,” Yang said.

“It also shows that those with low pTau217 levels are likely to stay amyloid-negative for several years,” he added.

These observations have important implications for both clinical research and eventual routine care. Although the authors have emphasised that it remains premature to recommend widespread pTau217 screening in older adults, the biomarker may offer immediate value as a stratification tool in clinical trials that target early-stage Alzheimer’s disease or attempt to prevent onset.

The ability to identify at-risk individuals years before conventional imaging changes could enable more efficient trial design and earlier therapeutic intervention. In the longer term, blood-based biomarkers such as pTau217 may integrate into standard health assessments, particularly if cost and accessibility advantages continue to favour blood testing over imaging modalities.

Amyloid PET scans remain expensive and resource-intensive, which has limited their use outside specialised centres. A scalable blood test that predicts disease trajectory could therefore transform screening pathways and broaden access to early detection.

“As the field is evolving quickly, we’re excited to see discoveries on the research side being rapidly translated to clinical application,” said Dr. Jasmeer Chhatwal, co-senior author and neurologist at the Mass General Brigham Neuroscience Institute.

“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,” he concluded.

For further reading please visit: 10.1038/s41467-026-71269-3