medwireNews: A plasma phosphorylated (p)-tau217 immunoassay offers comparative diagnostic accuracy for Alzheimer’s disease (AD) pathologies to that of cerebrospinal fluid (CSF) biomarkers, with the potential for accurate early screening with a reduced need for advanced confirmatory testing, shows a study published in JAMA Neurology.
Nicholas Ashton (Gothenburg University, Sweden) and colleagues analyzed data from three single-center observational cohorts to assess the utility of the commercially available immunoassay, ALZpath pTau217, to detect Alzheimer’s disease pathology.
Given that access to advanced testing such as CSF and positron emission tomography (PET) is often limited, they note that a blood biomarker that can “enhance an early and precise AD diagnosis has the potential to improve patient management and, ultimately, timely access to disease-modifying therapies.”
The study combined longitudinal and cross-sectional data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (2017–2021) and the Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort (2007–2020), as well as cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (2009–2021).
The 786 participants (mean age 66.3 years, 64.1% women), with or without cognitive impairment (4.3–57.9% and 42.1–95.7%, respectively), were grouped by confirmed amyloid β (Aβ) and tau status.
At baseline, 41.2–78.9% of patients were Aβ and tau negative, 3.3–24.6% were Aβ positive and tau negative, 6.8–55.5% were both Aβ and tau positive, and 0.3–1.0% were Aβ negative and tau positive.
The mean plasma p-tau217 level was 0.47–0.98 pg/mL at baseline and this “significantly increased in a stepwise manner in all cohorts,” say the investigators, being highest among those positive for both Aβ and tau and lowest in those negative for both.
The p-tau217 immunoassay was “highly accurate” at identifying elevated Aβ, at 92–96%, the team reports, as measured by PET in TRIAD and WRAP and by CSF Aβ42/40 in the SPIN cohort.
The immunoassay was similarly accurate at identifying tau pathology across the three cohorts, with an accuracy of 93–97%.
Moreover, the p-tau217 immunoassay outperformed existing imaging modalities in identifying AD pathology. For elevated Aβ, it was more accurate than PET-determined hippocampal atrophy (52–70% accurate), tau PET (72–86%), CSF p-tau181 (75%), and hippocampal volume (89%), while being comparable to CSF Aβ42/40 and CSF p-tau181/Aβ42.
The immunoassay also significantly outperformed comparators in predicting abnormal tau-PET burden, namely hippocampal volume in all three cohorts (65–91% accurate), CSF p-tau181 in WRAP only (69%), and Aβ PET in TRIAD (90%), but was comparable to Aβ PET in WRAP (96%).
When compared with other plasma biomarkers, the p-tau217 immunoassay alone or in combination with demographic variables, such as age, sex, and apolipoprotein E status, outperformed all comparators, including p-tau181, p-tau231, Aβ42/40, glial fibrillary acidic protein, and neurofilament light protein.
Ashton and colleagues also created three reference ranges, with low and high cutoff points (95% sensitivity, <0.4 pg/mL, and 95% specificity, >0.63 pg/mL, respectively), which “demonstrated high negative and positive concordance with β-amyloid status,” they note.
This left a small “intermediate” group of patients (12 to 23%) who would potentially require confirmatory advanced CSF or PET testing, reducing the current need by approximately 80%.
And examining up to 8 years of longitudinal outcome data (mean 5.22 years) from the WRAP cohort, plasma p-tau217 levels were found to increase only among individuals who had elevated Aβ at baseline, with the greatest increases occurring in those positive for both Aβ and tau. Data from the TRIAD group showed similar results, despite its shorter 1.90 years of follow-up.
Ashton et al comment that the cohorts from the study and the results may not be generalizable to all real-world scenarios; for example, two-thirds of patients did not have cognitive impairment.
However, they conclude: “These results emphasize the important role of plasma p-tau217 as an initial screening tool in the management of cognitive impairment by underlining those who may benefit from antiamyloid immunotherapies.”
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