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<\/a>Mass Normal Brigham researchers used long-term information and a blood check for the biomarker pTau217 to establish the earliest indicators of Alzheimer\u2019s<\/span> disease in cognitively healthy adults.<\/strong><\/p>\n A team of investigators at Mass General Brigham<\/a> reports that a blood test measuring plasma<\/span> phosphorylated tau 217 (pTau217), a biomarker linked to Alzheimer\u2019s disease, can forecast changes seen on amyloid PET scans as well as later cognitive decline in older adults who currently show no signs of impairment.<\/p>\n These findings suggest it may be possible to identify risk much earlier and with simpler tools, opening the door to earlier intervention. The study appears in Nature Communications<\/span><\/em>.<\/p>\n \u201cWe used to think that PET scan detection was the earliest sign of Alzheimer\u2019s disease progression, revealing amyloid accumulation in the brain 10 to 20 years before symptoms appear,\u201d said lead author Hyun-Sik Yang, MD, a neurologist with Mass General Brigham Neuroscience Institute and an associate member of the Broad Institute of MIT<\/span> and Harvard. \u201cBut now we are seeing that pTau217 can be detected years earlier, well before clear abnormalities appear on amyloid PET scans.\u201d<\/p>\n The U.S. Food and Drug Administration approved the first blood test for Alzheimer\u2019s disease last year, marking an important shift toward more accessible and less invasive diagnostic options compared with lumbar punctures and PET imaging. Building on that progress, Yang and colleagues provide further support that blood-based biomarkers can serve as early indicators of disease processes that were previously detectable only through imaging.<\/p>\n In this prospective cohort study, researchers tracked 317 cognitively healthy adults enrolled in the Harvard Aging Brain Study (HABS) for roughly eight years. Participants, aged 50 to 90, underwent repeated blood testing for pTau217 alongside amyloid and tau PET scans and detailed cognitive assessments. The team analyzed whether both initial levels and changes in pTau217 could anticipate future amyloid buildup, tau accumulation (the abnormal buildup of misfolded tau proteins inside brain neurons), and declines in cognitive performance.<\/p>\n The results showed a clear pattern. Individuals with higher pTau217 levels experienced more rapid development of Alzheimer \u2018s-related changes, even when their early brain scans appeared normal. In many cases, increases in the biomarker were observed before amyloid PET scans showed positive results, underscoring its sensitivity to early disease activity. By contrast, participants who began the study with low pTau217 levels were unlikely to show meaningful amyloid accumulation over the years that followed.<\/p>\n \u201cWhat 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,\u201d said Yang. \u201cIt also shows that those with low pTau217 levels are likely to stay amyloid-negative for several years.\u201d<\/p>\n Although pTau217 testing is not yet ready for routine clinical use, Yang and his colleagues see potential for it to play a key role in screening participants for prevention trials and identifying those at elevated risk before symptoms emerge. With further validation, such blood tests could become part of regular health monitoring and provide a lower-cost alternative to imaging-based methods.<\/p>\n \u201cAs the field is evolving quickly, we\u2019re excited to see discoveries on the research side being rapidly translated to clinical application,\u201d said co-senior author Jasmeer Chhatwal, MD, PhD, a neurologist with Mass General Brigham Neuroscience Institute. \u201cBy anticipating who\u2019s going to turn amyloid-positive in the future, we are trying to push back the clock to enable earlier Alzheimer\u2019s disease prediction.\u201d<\/p>\n Reference: \u201cPlasma phosphorylated tau 217 and longitudinal trajectories of A\u03b2, tau, and cognition in cognitively unimpaired older adults\u201d by Hyun-Sik Yang, Juliana A. U. Anzai, Wai-Ying Wendy Yau, Brian C. Healy, Andrea M. Rom\u00e1n 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, Philip B. Verghese, Joel B. Braunstein, Keith A. Johnson, Reisa A. Sperling and Jasmeer P. Chhatwal, 14 April 2026, Nature Communications<\/i>. This work was supported by grants K23 AG062750, K23 AG084868, P01 AG036694 (Harvard Aging Brain Study), and R01 AG071865 from the National Institute on Aging, as well as the Shelby Cullom Davis Charitable Fund\u2019s philanthropic gift.<\/p>\n Disclosure: Philip B. Verghese and Joel B. Braunstein are full-time employees of C2N Diagnostics LLC. Other authors declare no directly relevant conflict of interest.<\/p>\n Never miss a breakthrough: Join the SciTechDaily newsletter.<\/a><\/b>Blood marker signals disease earlier<\/h4>\n
Long-term study tracks early changes<\/h4>\n
Toward earlier Alzheimer\u2019s detection<\/h4>\n
DOI: 10.1038\/s41467-026-71269-3<\/a><\/p>\n
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