Breaking Barriers in Early Alzheimer's Disease Diagnosis: The Power of the In Vitro Diagnostic Elecsys pT181p Immunoassay in a Population Reflective of Real-world Clinical Practice
Sayuri Hortsch1, David Caley2, Patrick Menzel1, Christopher Rowe3, Mark Rapp4, Dag Aarsland5, Anna Burke6, Clara Quijano-Rubio7
1Roche Diagnostics GmbH, 2Roche Diagnostics Limited, 33 Australian Dementia Network Ltd, 4Berman Clinical, 5King's College London, 6Barrow Neurological Institute, 7Roche Diagnostics International Ltd
Objective:
This study validated a plasma tau phosphorylated at threonine 181 (pTau181p) cutoff using the Elecsys® Phospho-Tau (181P) assay (Roche Diagnostics) to rule out amyloid pathology in a diverse real-world cohort
Background:
Early diagnosis of Alzheimer’s disease (AD) is critical for optimizing management, outcomes, and quality of life. Current disease-modifying therapies target amyloid-β (Aβ), making amyloid pathology identification vital for diagnosis and treatment. Confirmatory tests like positron emission tomography (PET) and cerebrospinal fluid (CSF) are costly, invasive, and limited in availability. Blood-based biomarkers (BBBMs) show promise for improving access to early AD diagnosis. Validating BBBM performance in clinically representative populations is essential for practical application.
Design/Methods:
This prospective, multi-center study included 18 sites across the US, Europe, and Australia. Patients aged 55–80 with cognitive complaints or memory impairment of unknown causes were enrolled. Clinical stages included subjective cognitive decline (SCD), mild cognitive impairment (MCI), or mild dementia. Plasma pTau181p levels were measured using the Elecsys pT181p immunoassay. The pre-established cutoff of 0.934 pg/mL was validated against amyloid-PET and CSF pTau181/Aβ42 ratio results. Clinical performance metrics included the area under the curve (AUC), negative predictive value (NPV), and positive predictive value (PPV).
Results:
Of 787 patients, 650 had amyloid-PET results (43.8% male, mean age 69.3 years). Amyloid prevalence was 22.5% via PET and 28.0% via CSF. The AUC for pTau181p relative to amyloid-PET and CSF pTau181/Aβ42 ratio was 0.854 and 0.818, respectively. The NPV for amyloid-PET was 93.8%, independent of comorbidities, demonstrating strong rule-out performance.
Conclusions:
The pT181p immunoassay showed high performance in ruling out amyloid pathology across diverse clinical settings. Its utility could enhance access to early AD diagnosis, improving patient care and health outcomes while reducing economic burden.
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