AI Insight
Researchers developed a next-generation blood biomarker called brain-derived p-tau217%, which measures the proportion of circulating tau protein that originates specifically from the central nervous system and is phosphorylated at threonine 217. Tested across multiple cohorts including neuropathologically confirmed cases, neuroimaging-characterized patients, and memory clinic populations, this CNS-selective biomarker consistently outperformed conventional plasma p-tau217 and related measures in identifying Alzheimer's disease pathology, with greater effect sizes, higher discriminative accuracy, and stronger prediction of clinical progression over up to two decades of follow-up. Notably, the biomarker maintained high diagnostic performance in older adults with diabetes and cardiovascular disease, conditions known to reduce the specificity of standard p-tau217 measurements.
Why it matters
A blood test that more accurately and specifically detects Alzheimer's disease pathology, including in patients with common comorbidities, could substantially improve early diagnosis, patient selection for clinical trials, and monitoring of disease progression in routine clinical settings. This advance addresses a meaningful limitation of current biomarker approaches and may broaden equitable access to biologically supported Alzheimer's diagnosis across diverse patient populations.
⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Blood-based biomarkers have expanded access to biologically supported diagnosis of Alzheimer’s disease (AD), particularly through measurement of amyloid-beta (Abeta) and phosphorylated tau species. Among these, plasma tau phosphorylated at threonine 217 (p-tau217) is currently the leading biomarker recommended by clinical guidelines. However, circulating p-tau217 originates from both central nervous system (CNS) and peripheral tissues, potentially limiting specificity, particularly in individuals with common age-related comorbidities. Here we report a next-generation biomarker, brain-derived p-tau217%, which quantifies the proportion of circulating tau that is CNS-derived and phosphorylated at threonine 217. Across neuropathologically defined, Abeta- and tau-neuroimaging-characterized, and memory clinic cohorts, brain-derived p-tau217% consistently identified AD pathology and clinical AD with larger effect sizes, higher discriminative accuracy, and improved sensitivity and specificity, outperforming conventional non-CNS-selective plasma p-tau217, p-tau217/Abeta1-42 and p-tau217% alternatives as well as brain-derived-p-tau217 alone. Furthermore, the CNS-selective biomarker demonstrated more robust prediction of future clinical progression in individuals followed for up to two decades. Importantly, diagnostic performance remained high in older adults with diabetes and cardiovascular disease, populations in which standard p-tau217 showed reduced specificity. Moreover, superiority extended to comparisons against multiple CNS disease-related proteins in targeted proteomic analyses. These findings establish plasma brain-derived p-tau217% as a biologically grounded and clinically robust biomarker that advances molecular definition, detection, and prognosis of Alzheimer’s disease.
Source: CNS-selective plasma p-tau217 accurately captures Alzheimer's disease pathology and progression