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By Lucy Piper, medwireNews Reporter

medwireNews: A commercially available plasma phosphorylated (p)-tau217 immunoassay outperforms other biomarkers in accurately identifying biological Alzheimer’s disease (AD), suggest findings from a study across three observational cohorts.

“In primary care, it is estimated that more than 50% of patients with cognitive impairment remain undiagnosed or incorrectly diagnosed because of the lack of accessible and cost-effective tools,” which is why blood biomarkers are “set to revolutionize clinical care,” say Nicholas Ashton (Gothenburg University, Mölndal Hospital, Sweden) and colleagues.

They add: “As anti-Aβ [amyloid β] trials move toward targeting a preclinical population with lower prevalence of Aβ abnormalities, a cost-effective strategy becomes paramount.”

They found that the p-tau217 immunoassay (ALZpath pTau217) was 92–96% accurate at identifying elevated Aβ and 93–97% accurate at identifying tau pathology across three cohorts, comprising a total of 786 participants with and without cognitive impairment (4.3–57.9% and 42.1–95.7%, respectively) who were aged a mean of 64 years and were predominantly women (64.1%).

The three single-centre cohorts were the Translational Biomarkers in Aging and Dementia (TRIAD), the Wisconsin Registry for Alzheimer’s Prevention (WRAP), and the Sant Pau Initiative on Neurodegeneration (SPIN).

Plasma Aβ was determined by positron emission tomography (PET) in TRIAD and WRAP. In SPIN, it was determined by PET in a subset of patients, but mainly with cerebrospinal fluid (CSF) Aβ42/40. Aβ-PET positivity was defined as a centiloid value greater than 24 units and tau positivity as a meta-temporal region of interest greater than 1.24 units in TRIAD and 1.3 units in WRAP.

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 at baseline was 0.47–0.98 pg/mL and this increased in a stepwise manner, being highest among those positive for both Aβ and tau and lowest in those negative for both.

The researchers highlight that the discriminative ability of the p-tau217 immunoassay extended to identifying normal tau pathology among the participants who were Aβ positive, with an accuracy of 87–90%.

“This is particularly important as antiamyloid therapies may be less effective in patients with advanced tau pathology,” they explain in JAMA Neurology.

When the team compared the ability of the p-tau217 immunoassay to identify AD pathology with existing CSF biomarkers, they found that for determining Aβ PET it significantly outperformed hippocampal atrophy (52–89% accurate), tau PET (72–86%) and CSF p-tau181 (75%), and it was comparable to CSF Aβ42/40 and CSF p-tau181/Aβ42.

The findings were similar for determining abnormal tau pathology, with the p-tau217 immunoassay significantly outperforming hippocampal volume in all three cohorts (65–91% accurate), CSF p-tau181 in WRAP only (69%) and Aβ PET in TRIAD (90%), while being comparable in WRAP (96%).

The p-tau217 immunoassay also outperformed other plasma biomarkers for detecting AD pathology, including p-tau181, p-tau231, Aβ42/40, glial fibrillary acidic protein and neurofilament light.

Ashton and colleagues point out that while the performance of some of these other plasma biomarkers “relied more heavily” on variables such as age and apolipoprotein E status, “only modest improvements in diagnostic accuracy” were seen when the p-tau217 immunoassay was combined with these variables.

The researchers applied a three-range approach to create lower (95% sensitivity, <0.4 pg/mL) and upper (95% specificity, >0.63 pg/mL) cutoff points that improved the agreement of Aβ-positive results across the three cohorts, while maintaining similar agreement on the number of Aβ-negative results.

This led to a “substantial reduction” of approximately 80% in the proportion of “intermediate” patients who would then need confirmatory CSF or PET testing, say Ashton et al.

The findings from up to 8 years of longitudinal sampling also suggest that the p-tau217 immunoassay can be used to monitor Aβ pathology over time, with increases measured only in individuals with elevated Aβ at baseline, and the greatest increases occurring in those positive for both Aβ and tau.

“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,” the investigators conclude.


News stories are provided by medwireNews, which is an independent medical news service provided by Springer Healthcare Ltd. © 2024 Springer Healthcare Ltd, part of the Springer Nature Group

JAMA Neurol 2024; doi:10.1001/jamaneurol.2023.5319

https://pubmed.ncbi.nlm.nih.gov/37723208/