Study highlights potential of p-tau217 assays in Alzheimer's clinical trials and diagnosis

By Tarun Sai LomteMar 14 2024Reviewed by Lily Ramsey, LLM

In a recent study published in eBioMedicine, researchers compared the performance of two commercial phospho-tau217 (p-tau217) assays.

Study: Comparison of two plasma p-tau217 assays to detect and monitor Alzheimer’s pathology. Image Credit: UnderhilStudio/Shutterstock.com

Background

Quantification of tau and amyloid pathologies has enabled Alzheimer’s disease (AD) diagnosis. Recent reports of blood-based biomarkers can transform AD diagnosis. The growing availability of disease-modifying treatments for AD warrants the need for accessible, scalable biomarkers.

Determination of amyloid pathology through biomarker investigations is required to assess eligibility for anti-amyloid treatment.

Further, plasma biomarkers can aid in the identification of advanced tau pathology. p-tau217 is a potential blood-based biomarker for AD due to its strong correlations with tau and amyloid pathologies, diagnostic performance, and equivalence with established cerebrospinal fluid (CSF) biomarkers.

Determining whether distinct p-tau217 biomarkers are consistent in AD detection will increase their clinical utility.

About the study

In the present study, researchers compared the diagnostic performance of the Janssen p-tau217+ assay and ALZpath p-tau217 assay. Analyses were performed on a convenience sample from the Translational Biomarkers of Aging and Dementia (TRIAD) cohort.

The study included participants with tau and amyloid positron emission tomography (PET) imaging and plasma specimens for p-tau217 assays. Data were collected from October 2017 to August 2022.

Clinical diagnosis was performed before acquiring biomarker data in the cohort; cognitively unimpaired (CU) individuals had clinical dementia rating (CDR) and mini-mental state examination scores of 0 and > 24, respectively.

Subjects with mild cognitive impairment (MCI) had a CDR score of 0.5. Participants with AD dementia had a CDR score ≥ 0.5. Non-AD patients were those with dementia but without amyloid pathology on PET.

Plasma (ALZpath and Janssen) and CSF (ALZpath) p-tau217 assays were performed. PET imaging data and participants’ magnetic resonance imaging (MRI) were processed. Tau and amyloid-beta (Aβ) standardized uptake value ratios (SUVRs) were calculated. SUVR ≥ 1.24 indicated tau positivity.

Regional tau PET was quantified in neocortical and medial temporal regions. Besides, subjects were classified into PET-based Braak stages.

Sex proportions and age were compared between groups using the chi-squared test and analysis of variance. Spearman rank tests determined correlations between biomarkers.

Analysis of covariance was performed to compare biomarker levels between groups, and the results were adjusted for sex and age. Voxel-wise regression analyses were performed to investigate associations between plasma markers and tau and amyloid PET, adjusted for sex and age.

Findings

The researchers included 294 participants. p-tau217 concentrations were assessed in young individuals, CU older adults, MCI subjects, people with AD dementia, and those with non-AD neurodegeneration. Plasma levels of p-tau217 increased with the clinical severity.

Amyloid-negative MCI subjects and those with non-AD neurodegenerative diseases exhibited low plasma p-tau217 levels in both assays.

Both assays exhibited robust correlations with CSF p-tau217 and amyloid PET SUVR. Voxel-wise analyses showed that the two assays had similar topographical association patterns between plasma amyloid PET and p-tau217.

Likewise, the two assays strongly correlated with tau PET in the neocortical and medial temporal regions; they also correlated well with tau PET SUVR.

Voxel-wise analyses revealed that both assays had similar topographical association patterns between plasma p-tau217 and tau PET.

Both plasma p-tau217 assays were in agreement in 92% of cases. Further, both assays exhibited remarkable agreement in identifying amyloid PET-positive subjects and those with biomarker-defined AD.

The diagnostic performance of plasma biomarkers to identify amyloid PET positivity in CU subjects and AD in those with cognitive impairment was assessed. The two assays effectively detected amyloid PET positivity and biological AD.

A subset of participants had plasma and tau PET data at ≥ one additional time point, thereby allowing the calculation of the annual change in biomarkers. The annual change in plasma p-tau217 assays correlated well with annual changes in neocortical tau PET.

Conclusions

The researchers compared two p-tau217 assays and noted robust and similar associations with neocortical amyloid PET.

Their diagnostic performance was identical for amyloid PET positivity in asymptomatic individuals and tau and amyloid positivity in those with cognitive impairment. The findings suggest that p-tau217 assays could be suitable for diagnosing and monitoring AD pathology.