The increasing number of patients suffering from dementia caused by Alzheimer’s disease (AD) is a significant challenge for society and requires action by healthcare professionals and researchers worldwide. One important aspect of combatting the disease is confirming an early and accurate diagnosis. Currently, such a diagnosis can be made using specific positron emission tomography (PET) or cerebrospinal fluid analysis of biomarkers such as ß-amyloid (Aß) or tau.1 In particular, tau phosphorylated at threonine 217 (P-tau217) was recently found to be an accurate biomarker for diagnosis.2 Sebastian Palmquvist (Department of Clinical Sciences, Lund University, Sweden) and his colleagues tried to go one step further and tested whether they could utilise the plasma levels of P-tau217 as a diagnostic biomarker for AD. In July 2020, they published their ground-breaking results in JAMA.1
Three different cohorts on the way to success
To determine whether plasma P-tau127 could be a reliable biomarker for the detection of AD, the researchers looked at three different cross-sectional cohorts: one Arizona, United States-based cohort including participants both with and without AD; one Swedish cohort including healthy participants, patients with mild cognitive impairment, patients with AD dementia, and patients with other neurodegenerative diseases; and one Colombian cohort including participants with or without a specific AD-associated PSEN1 mutation.1 In total, the study examined 1,402 participants from all three cohorts, with the goal to determine the discriminative accuracy of plasma P-tau127 for AD and to determine its association with tau pathology.
Plasma P-tau217 found to be a reliable biomarker for Alzheimer’s disease
Dr Palmquvist and his colleagues found consistently positive results in all three cohorts.1 In the Arizona-based cohort, the plasma levels of P-tau127 successfully differentiated non-AD from AD patients. Furthermore, P-tau127 plasma levels distinguished clinical AD dementia patients from patients with other neurodegenerative diseases in the Swedish cohort, and abnormal from normal tau-specific PET scans. In the Colombian cohort, plasma P-tau127 levels were significantly higher in PSEN1 mutation carriers compared with non-carriers. Overall, the accuracy of the P-tau127 plasma test was significantly higher than that of other available plasma- and MRI-based tests, but did not significantly differ from cerebrospinal fluid or PET measurements.
The authors state that their “results indicate that plasma P-tau217 might be useful in the differential diagnosis of patients with cognitive impairment”1, which might be quite an understatement. A reliable, plasma-based test for AD could change clinical practice and early detection possibilities, which could be especially useful in healthcare facilities with limited access to PET or cerebrospinal fluid examinations. Also important to mention are the significantly lower costs, as well as the less-invasive nature of plasma testing compared to current standard diagnostic tests. However, the researchers now need to further develop, optimise, and validate the assay to pave the way for its use in clinical practice. We are not quite there yet, but definitely a big step closer.