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Background: Blood-based biomarkers of Alzheimer's disease (AD) have become increasingly important as scalable tools for diagnosis and determining clinical trial eligibility. P-tau217 is the most promising due to its excellent sensitivity and specificity for AD-related pathological changes.
Methods: We compared the performance of two commercially available plasma p-tau217 assays (ALZpath p-tau217 and Janssen p-tau217+) in 294 individuals cross-sectionally. Correlations with amyloid PET and tau PET were assessed, and Receiver Operating Characteristic (ROC) analyses evaluated both p-tau217 assays for identifying AD pathology.
Findings: Both plasma p-tau217 assays were strongly associated with amyloid and tau PET. Furthermore, both plasma p-tau217 assays identified individuals with AD vs other neurodegenerative diseases (ALZpath AUC = 0.95; Janssen AUC = 0.96). Additionally, plasma p-tau217 concentrations rose with AD severity and their annual changes correlated with tau PET annual change.
Interpretation: Both p-tau217 assays had excellent diagnostic performance for AD. Our study supports the future clinical use of commercially-available assays for p-tau217.
Funding: This research is supported by the Weston Brain Institute, Canadian Institutes of Health Research (CIHR), Canadian Consortium on Neurodegeneration in Aging, the Alzheimer's Association, Brain Canada Foundation, the Fonds de Recherche du Québec - Santé and the Colin J. Adair Charitable Foundation.
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http://dx.doi.org/10.1016/j.ebiom.2024.105046 | DOI Listing |
Neurology
October 2025
Alzheimer's Disease and Other Cognitive Disorders Unit, Department of Neurology, Hospital Clínic de Barcelona, Fundació Recerca Clínic Barcelona-IDIBAPS, Spain.
Background And Objectives: α-Synuclein seed amplification assays (αSAAs) can improve the diagnosis of synucleinopathies and detect α-synuclein (αSyn) copathology in vivo in clinical practice. We aimed to evaluate the diagnostic performance of αSAA for detecting αSyn in CSF for diagnosing dementia with Lewy bodies (DLB) in a clinical cohort of cognitively impaired individuals. We explored how the coexistence of Alzheimer disease (AD) and αSyn pathology influences biomarker levels and clinical profiles.
View Article and Find Full Text PDFClin Nucl Med
September 2025
Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Gangnam-gu, Seoul, Republic of Korea.
Background: Alzheimer disease (AD) is characterized by amyloid-β plaques (A), tau tangles (T), and neurodegeneration (N), collectively defining the ATN framework. While imaging biomarkers are well-established, the prognostic value of plasma biomarkers in predicting cognitive decline remains underexplored. This study compares plasma and imaging A/T/N biomarkers in predicting cognitive decline and evaluate the impact of combining biomarkers across modalities.
View Article and Find Full Text PDFACS Chem Neurosci
September 2025
School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-sen University, Shenzhen 518107, China.
Post-translational modifications, such as truncation facilitated by proteases and phosphorylation mediated by protein kinases, play pivotal roles in Tau protein function and cellular processes. The detection of distinct Tau forms in plasma has garnered significant interest in the scientific and translational communities. We discovered monoclonal antibodies (mAbs) using the hybridoma technique by immunizing mice with different Tau proteins.
View Article and Find Full Text PDFmedRxiv
August 2025
Department of Neurology, Perelman School of Medicine, University of Pennsylvania; 3600 Spruce Street, Philadelphia, PA 19104.
Objective: Plasma biomarkers of Alzheimer's disease (AD) pathology are frequently tested in specialized research settings, limiting generalizability of findings. Using electronic health records and banked plasma, we evaluated plasma biomarkers - phosphorylated tau 217 (p-tau), β-amyloid 1-42/1-40 (Aβ/Aβ) and p-tau/Aβ - in a real-world, diverse clinical population with multimorbidities.
Methods: Participants (n=617; 44% Black/African American; 41% female) were selected from the University of Pennsylvania Medicine BioBank with plasma assayed using Fujirebio Lumipulse.
Alzheimers Dement
September 2025
Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.
Introduction: Plasma biomarkers' utility for predicting incident mild cognitive impairment (MCI) remains unclear. We evaluated associations of plasma Alzheimer's disease (AD) biomarkers and amyloid positron emission tomography (PET) with transitions from cognitively unimpaired (CU) to MCI in the Mayo Clinic Study of Aging (MCSA) and BioFINDER-2 studies.
Methods: Associations of continuous baseline plasma biomarker levels and amyloid PET Centiloid with progression to MCI, adjusting for age, sex, and education, were evaluated with Cox proportional hazards models.