p-tau217 has emerged as a revolutionary blood biomarker for Alzheimer’s disease. It offers an affordable and accurate way to detect pathological changes in AD at all stages of the disease. With further studies and improvements in assay availability, p-tau217 has the potential to transform the diagnosis and treatment of AD, benefiting millions of people worldwide.
Alzheimer’s disease (AD) is a progressive neurodegenerative condition that affects millions of people worldwide. With advancing research, blood biomarkers have gained prominence as important tools to improve the diagnosis, monitoring, and treatment of this disease.
A biomarker is a measurable biological characteristic that indicates a normal process, a condition or disease, or the body’s response to a treatment. It can be detected in body fluids, tissues, or imaging studies.
These tools promise to reduce the need for invasive and expensive tests, such as cerebrospinal fluid (CSF) analysis or positron emission tomography (PET), which are usually only available in specialized centers.
Blood-based biomarkers offer a less invasive, more affordable, and scalable way to assess the presence of Alzheimer’s disease. They enable early and accurate identification of the condition, especially in settings where advanced testing is not available.
This means that more patients can be diagnosed quickly and receive appropriate treatment at an earlier stage when interventions can be most effective. Among the various blood-based biomarker candidates, phosphorylated tau (p-tau) has emerged as the most promising.
In particular, the version phosphorylated at threonine 217 (p-tau217) has shown highly accurate results in identifying AD and distinguishing it from other neurodegenerative disorders. p-tau plays a key role in the diagnosis of AD because it is directly associated with two of the disease’s key pathological processes: the deposition of amyloid beta (Aβ) plaques.
These plaques accumulate between neurons and are a hallmark of AD. Furthermore, it promotes neurofibrillary tangles, which are formed by abnormal aggregates of tau; these tangles destroy neuronal connections and cell death.
Tau Protein Disrupts Molecular Transport in Neurons in Alzheimer’s Disease
p-tau217 has been shown to outperform in identifying AD, even in early or asymptomatic stages. It is particularly useful because it correlates with Aβ levels and the severity of neurofibrillary tangles.
Studies show that this biomarker can identify AD-related brain changes with greater than 90% accuracy.
Although other biomarkers, such as the amyloid β 42/40 ratio (Aβ42/40), are also used, they have limitations when evaluated in the blood. p-tau217, on the other hand, offers more consistent and accurate results.
Compared to other p-tau subtypes (such as p-tau181 and p-tau231), p-tau217 exhibits more significant changes in blood levels, making it easier to detect the disease, even in cases of mild cognitive impairment (MCI).
Recent research has examined the efficacy of p-tau217 in three large observational cohorts:
TRIAD: Included 268 participants, with a balance between individuals without cognitive impairment and those with AD or other types of dementia.
WRAP: Included 323 individuals, mostly without cognitive impairment.
SPIN: With 195 participants, focused on individuals with AD and MCI due to the disease.
The studies confirmed that p-tau217 is highly effective in detecting amyloid and tau pathology, comparable to invasive methods such as CSF analysis or PET.
The advances in the use of p-tau217 are especially important at a time when anti-amyloid therapies are beginning to be used to treat AD.
With a reliable blood-based biomarker, it is possible to identify patients who will benefit most from these therapies. Furthermore, the use of standardized reference ranges for p-tau217 levels may reduce the need for confirmatory testing, thereby accelerating diagnosis.
The data also show that p-tau217 levels increase over time in individuals with high Aβ burden, reflecting disease progression. This suggests that p-tau217 could be used not only for initial diagnosis but also for monitoring the progression of AD.
Despite its promising potential, the availability of commercial assays to measure p-tau217 is still limited. One of the current goals is to expand access to these tests for research and clinical practice. Future studies will continue to explore the utility of p-tau217 in different populations and its integration with other diagnostic tools.
p-tau217 has emerged as a game-changing blood-based biomarker for Alzheimer’s disease. It offers an affordable and accurate way to detect pathological changes in AD at all stages of the disease.
With further studies and improvements in assay availability, p-tau217 has the potential to transform the diagnosis and treatment of AD, benefiting millions of people worldwide.
READ MORE:
Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer's Disease Pathology
Hanna Huber, Laia Montoliu-Gaya, Wagner S. Brum, Jakub Vávra, Yara Yakoub, Haley Weninger, Silke Kern, Barbara Borroni, Anne Corbett, Oskar Hansson, Xavier Morató, Henrik Zetterberg, Kaj Blennow, and Nicholas J. Ashton
JAMA Neurol. 2024;81(3):255-263.
doi:10.1001/jamaneurol.2023.5319
Abstract:
Phosphorylated tau (p-tau) is a specific blood biomarker for Alzheimer's disease (AD) pathology, with p-tau217 considered to have the most utility. However, the availability of p-tau217 tests for research and clinical use has been limited. Expanding access to this highly accurate AD biomarker is crucial for wider evaluation and implementation of AD blood tests. To determine the utility of a novel and commercially available immunoassay for plasma p-tau217 to detect AD pathology and evaluate reference ranges for abnormal amyloid β (Aβ) and longitudinal change across 3 selected cohorts. This cohort study examined data from 3 single-center observational cohorts: cross-sectional and longitudinal data from the Translational Biomarkers in Aging and Dementia (TRIAD) cohort (visits October 2017–August 2021) and Wisconsin Registry for Alzheimer’s Prevention (WRAP) cohort (visits February 2007–November 2020) and cross-sectional data from the Sant Pau Initiative on Neurodegeneration (SPIN) cohort (baseline visits March 2009–November 2021). Participants included individuals with and without cognitive impairment grouped by amyloid and tau (AT) status using PET or CSF biomarkers. Data were analyzed from February to June 2023. Magnetic resonance imaging, Aβ positron emission tomography (PET), tau PET, cerebrospinal fluid (CSF) biomarkers (Aβ42/40 and p-tau immunoassays), and plasma p-tau217 (ALZpath pTau217 assay). Accuracy of plasma p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status. The study included 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%] and 282 males [35.9%]). High accuracy was observed in identifying elevated Aβ (area under the curve [AUC], 0.92-0.96; 95% CI, 0.89-0.99) and tau pathology (AUC, 0.93-0.97; 95% CI, 0.84-0.99) across all cohorts. These accuracies were comparable with CSF biomarkers in determining abnormal PET signals. The detection of abnormal Aβ pathology using a 3-range reference yielded reproducible results and reduced confirmatory testing by approximately 80%. Longitudinally, plasma p-tau217 values showed an annual increase only in Aβ-positive individuals, with the highest increase observed in those with tau positivity. This study found that a commercially available plasma p-tau217 immunoassay accurately identified biological AD, comparable with results using CSF biomarkers, with reproducible cut-offs across cohorts. It detected longitudinal changes, including at the preclinical stage.
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