Promising Blood Test Shows High Accuracy in Alzheimer’s Detection
Researchers at the University of Gothenburg, along with colleagues from the University of Lund and Montreal, Canada, have presented a new blood test called p-tau217 that shows promise as a biomarker for Alzheimer’s disease. This innovative test, when used in a two-step workflow, demonstrates high accuracy in either identifying or excluding brain amyloidosis, a crucial and early pathology associated with Alzheimer’s.
Over the past few years, there has been significant focus on developing blood biomarkers that can aid in the identification of Alzheimer’s disease (AD). One such biomarker that has been extensively researched and developed is the tau protein, particularly its phosphorylated variant known as p-tau. These blood-based p-tau biomarkers, specifically p-tau217, have shown great potential as valuable tools for screening patients with memory issues or other early cognitive symptoms that may indicate the presence of Alzheimer’s.
However, a major concern has been the possibility of false positives (positive test results in individuals without AD) and false negatives (negative test results in individuals who actually have AD) when classifying early-stage patients as either having or not having Alzheimer’s. This dilemma raises ethical and psychological concerns regarding misdiagnosis, as well as the high costs and potential risks associated with initiating treatments for individuals who do not have the disease.
To address these concerns, the scientists at the University of Gothenburg, together with their colleagues, have developed a novel strategy for the clinical implementation of blood biomarkers. This two-step workflow involves a diagnostic model in the first step, which utilizes plasma p-tau217, age, and APOE e4 to stratify patients with mild cognitive impairment (MCI) based on their risk of amyloid PET positivity. In the second step, confirmatory testing with the CSF Ab42/40 ratio (or amyloid EPT) is conducted only for those with uncertain outcomes from the first step.
The performance of this two-step model was evaluated on 348 MCI participants from the Swedish BioFINDER studies and validated on an independent TRIAD cohort from McGill University in Montreal. The analysis of plasma p-tau217 was carried out using an independent method.
The model was assessed using different thresholding strategies to categorize participants into groups with low, intermediate, or high risk of having AD-type pathology (Aβ positive). With a stringent lower probability threshold of 97.5% sensitivity to avoid missing the detection of Aβ positive patients, the false negative rate was as low as 6.6%. Similarly, with a stringent 97.5% specificity threshold to avoid classifying Aβ negative patients as high risk, the false positive rate was only 2.3%.
At these stringent sensitivity/specificity thresholds, 41% of patients fell into the intermediate risk group, compared to 29% at the 95% thresholds. Further evaluation of this group using CSF Aβ42/40 exhibited a high agreement of 86% with amyloid PET results. These findings were confirmed in an independent cohort of patients from McGill University.
Overall, this study presents a two-step model based on blood plasma p-tau217 for risk stratification of MCI patients, categorizing them as having high, low, or intermediate risk of brain amyloidosis and early AD pathology. The blood test used in the first step demonstrates highly accurate identification of high-risk patients, who can be given a diagnosis and initiated on symptomatic treatments, or referred to specialist clinics for possible disease-modifying treatment in the future. Furthermore, the low-risk group can have AD confidently excluded, leading to substantial cost savings by reducing the need for confirmatory CSF or PET testing at specialist clinics.
