Plasma Phospho-Tau217: A Promising Biomarker for Alzheimer Disease


Recent studies of the CSF P-tau217 blood biomarker suggest it may help to simplify the diagnosis of Alzheimer disease.

Oskar Hansson, MD, PhD, associate professor, Lund University

Oskar Hansson, MD, PhD

A recent study has proposed that plasma phospho-Tau217 (P-tau217) can be used as a new early biomarker for Alzheimer Disease (AD) after finding P-tau217 levels increased in early preclinical AD before tau could be detected by positron emission tomography (tau-PET positivity). 

Plasma P-tau217 levels were increased in cognitively unimpaired participants with abnormal amyloid-β (Aβ)-PET but normal tau-PET in the entorhinal cortex (median, 2.2 pg/mL; interquartile range [IQR], 1.5–2.9) compared with the group of cognitively unimpaired participants with normal Aβ-PET and normal tau-PET (0.7 pg/mL; IQR, 0.3–1.3pg/mL).1

Shorena Janelidze, PhD, assistant researcher, Clinical Memory Research Unit, Lund University, and principal author of the research paper, outlined the motivations behind the study, stating, “blood-based biomarkers are more suitable than cerebrospinal fluid (CSF) or PET for implementation in primary cares settings worldwide and may reduce the costs of clinical trials by improving selection and stratification of participants and monitoring of treatment response.”

The authors, including Oskar Hansson, MD, PhD, associate professor, Lund University, investigated the biomarker in 490 participants with a mean age of 65.9 years. Study participants included neurologically and cognitively healthy control individuals and those with subjective cognitive decline or mild cognitive impairment (MCI) from the prospective and longitudinal Swedish Bio FINDER-2 study who had previously been assessed with both tau-PET and Aβ-PET imaging.

READ MORE: First Widely Accessible Alzheimer Disease Blood Test Reaches Clinic

Elizabeth H, Thijssen, MSc, commented on the study in a related editorial, writing that “the current study by Janelidze et al and other recent studies provide proof of concept that brain Aβ and phosphorylated tau can be detected in plasma with high accuracy that is essentially equivalent to that of CSF or PET. The standardization and reproducibility of plasma assays will be accelerated by lessons learned from the development of CSF biomarkers and by international AD fluid biomarker consortia focused on this mission.”2

Of the 314 cognitively unimpaired participants, 80.3% (n = 252) were Aβ-PETnegative/tau-PET negative, 15% (n = 47) were Aβ-PETpositive/tau-PETnegative, 4.5% (n = 14) were Aβ-PETpositive/tau-PETpositive, and 0.3% (n = 1) were Aβ-PETnegative/tau-PETpositive. The researchers confirmed the correlation of plasma P-tau217 with CSF P-tau217 in Aβ-PETpositive cognitively unimpaired patients (P <.001) and in Aβ-PETpositive patients with MCI (P <.001). 

Recent studies have shown CSF P-tau217 to be a more accurate biomarker than the older CSF P-tau181 biomarker for Alzheimer disease. Traditional methods of Alzheimer diagnosis consist of measuring tau-aggregates in CSF, but P-tau217 and P-tau181 have been found to be present years before tau-PET positivity.

Of cognitively unimpaired participants who were discordant for these 2 measures, 94.7% (n = 36) were positive for plasma P-tau217 and negative for tau-PET. Event based modeling performed on these measures predicted that plasma and CSF P-tau217 would change before tau-PET positivity in cognitively unimpaired participants and those with MCI.

Plasma and CSF P-tau levels were increased at lower Aβ-PET levels before an increase of tau-PET. Plasma P-tau217 significantly mediated the association between Aβ-PET and tau-PET (partial mediation, 76.4%). Longitudinal change was also assessed and Janelidze and colleagues found that the yearly increase in tau-PET levels was higher in individuals with high baseline levels of plasma P-tau217 (median standardized uptake value ratio [SUVR], 0.029; IQR, -0.006 to 0.041) than those with low baseline levels of plasma P-tau217 (median SUVR, -0.001; IQR, -0.021 to 0.020; P = .02). These values correspond to a 2.2% per year SUVR increase from baseline in those with P-tau217 positivity.

“These findings suggest that plasma P-tau217 is a promising biomarker of early AD that might be particularly useful for patient selection and as an outcome measure to monitor drug responses in clinical trials including individuals with preclinical AD,” Janelidze and colleagues concluded.

1. Janelidze S, Berron D, Smith R, et. al. Associations of plasma phospho-tau217 levels with tau positron emission tomography in early Alzheimer disease. JAMA Neurol. Published online November 9, 2020. doi:10.1001/jamaneurol.2020.4201
2. Thijssen EH, Rabinovici GD. Rapid progress toward reliable blood tests for Alzheimer disease. JAMA Neurol. Published online November 9, 2020. doi:10.1001/jamaneurol.2020.4200
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