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CTAD 2022 | Performance of plasma p-tau181 as a community-based screening tool for AD clinical trials

In previous research, plasma phosphorylated-tau181 (p-tau181) has been demonstrated as a successful early biomarker to predict Alzheimer’s disease (AD) pathology. Milica Kramberger, MD, PhD, University Medical Centre Ljubljana, Ljubljana, Slovenia, shares results from a recent pilot study testing the potential of plasma p-tau181 in identifying self-referred individuals at early asymptomatic and symptomatic stages of AD. In subjects with cognitive complaints in the last 3-5 years, plasma p-tau181 levels and APOE status were compared to amyloid-β (Aβ) positivity, determined by cerebrospinal fluid (CSF) Aβ42/40 ratio. A prediction model was developed using p-tau181 and APOE status, and the accuracy of detection of underlying AD was tested at different specificity thresholds. Of those who had a p-tau181 level above the screening threshold and went on to undergo a lumbar puncture, amyloid positivity was confirmed in 50%. Using the prediction model, probabilities of CSF Aβ positivity in screened cases were 40%, 34% and 19% at the 85%, 90% and 95% specificity thresholds, respectively. The study concluded that only at a 95% specificity threshold could plasma p-tau181 substantially reduce the rate of Aβ-negative CSF results, although with this threshold about a third of CSF Aβ-positive patients were identified as false-negatives. Dr Kramberger believes that more studies are needed to optimize the use of plasma p-tau181 in clinical trial screening and how it could be used in combination with other biomarkers. This interview took place at the Clinical Trials on Alzheimer’s Disease Congress 2022 in San Francisco.

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