Advancing Alzheimer’s Disease Pathology Detection with Simoa® ALZpath p-Tau217 Assay thumbnail image

Advancing Alzheimer’s Disease Pathology Detection with Simoa® ALZpath p-Tau217 Assay

In the pursuit of effective diagnostics and treatments for Alzheimer’s disease (AD), blood-based biomarkers have emerged as transformative tools. Offering scalability, accessibility, and accuracy, they hold promise to revolutionize clinical evaluation, trial recruitment, and disease evaluation. A recent groundbreaking study1 published in JAMA Neurology showcases the diagnostic performance and utility of our commercially available plasma Simoa® ALZpath p-Tau 217 immunoassay, shedding light on its potential role in transforming AD pathology detection.  

A Step Forward in AD Diagnosis: p-Tau 217 Blood Test 

Phosphorylated tau (p-Tau) has emerged as a promising blood-based biomarker, surpassing the limitations of cerebral spinal fluid (CSF) biomarkers like amyloid β (Aβ) 42/20 ratio. Among the p-Tau biomarkers currently being investigated, p-Tau 217 has demonstrated superior capability in detecting AD pathology in patients with mild cognitive impairment (MCI) as well as differentiating AD from other neurological conditions2,3. Additionally, studies have shown that p-Tau 217 blood levels correlate with cognitive decline and brain atrophy in individuals with elevated Aβ pathology4,5. However, the widespread adoption of p-Tau 217 blood tests is hindered due to the limited availability of commercial assays. This study aimed to evaluate the utility of the commercially available Simoa® ALZpath pTau217 assay in detecting AD pathology and to establish reference ranges of plasma p-Tau 217 levels corresponding to abnormal amyloid positron emission tomography (PET) and CSF measures. 

Assessing the Simoa® ALZpath p-Tau 217 Assay 

The study1 examined data from a total of 786 participants from three single-center observational cohorts: Translational Biomarkers in Aging and Dementia (TRIAD), Wisconsin Registry for Alzheimer’s Prevention (WRAP), and Sant Pau Initiative on Neurodegeneration (SPIN). Participants, including individuals with and without cognitive impairment, were grouped according to Aβ and tau (AT) status using PET or CSF biomarkers. 

Plasma Aβ 42/40, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) levels were measured in all three cohorts using the Simoa® Human Neurology 4-Plex E (N4PE) assay. Plasma p-Tau 231 and p-Tau 181 levels were measured with an in-house Simoa® assay developed by the University of Gothenburg6,7 with Simoa® Homebrew Custom Assay Development, except in WRAP where plasma p-Tau 181 was measured by the Simoa® p-Tau 181 assay. Plasma p-Tau 217 levels were measured using the Simoa® ALZpath p-Tau 217 assay. All plasma levels were analyzed on Quanterix’s HD-X™ Automated Immunoassay Analyzer

Diagnostic Accuracy of Simoa® ALZpath p-Tau 217 Assay Comparable to CSF Biomarkers 

In a comprehensive effort to evaluate the performance of the Simoa® ALZpath p-Tau 217 assay, samples from 786 individuals with and without cognitive impairment from three cohorts representing the AD spectrum were analyzed. Notably, the results were remarkably consistent across cohorts and indicate1

  • Plasma p-Tau 217 significantly increased in a stepwise manner when stratified by AT status, regardless of clinical diagnosis, with the highest p-Tau 217 levels in the A+T+ group. 
  • Plasma p-Tau 217 demonstrated high accuracy in discriminating abnormal Aβ and tau PET status. 
  • Plasma p-Tau 217 detected Aβ and tau PET status, as well as differentiate A+T+ from A+T individuals, comparably to CSF biomarkers. 
  • Plasma p-Tau 217 outperformed all other plasma biomarkers for predicting Aβ and tau PET status. 

Overall, this study suggests that when utilizing the Simoa® ALZpath p-Tau 217 assay, plasma p-Tau 217 demonstrates high diagnostic accuracy for detecting AD pathology, and its performance is comparable to CSF fluid biomarkers. 

Establishing Reference Ranges for Plasma p-Tau 217 and Longitudinal Changes 

The researchers established a 3-range reference for Aβ positivity: 

  • Plasma p-Tau positive: >0.63 pg/mL 
  • Plasma p-Tau intermediate: 0.4 – 0.63 pg/mL 
  • Plasma p-Tau negative: <0.4 pg/mL 

This three-range reference achieved a high overall percent agreement (OPA) across the three cohorts. Additionally, approximately 20% of individuals fell into the plasma p-Tau 217 intermediate range and thus, in practice, could be referred for confirmatory testing with CSF or PET.  

These results suggest that the use of this three-range plasma p-Tau 217 reference range may potentially reduce the need for confirmatory testing by approximately 80%. 

In up to 8 years of longitudinal sampling, plasma p-Tau 217 levels increased annually in Aβ positive individuals only.  Additionally, the largest change in plasma p-Tau 217 levels was in individuals positive for both Aβ and tau positivity (A+T+). 

Impact on AD Pathophysiology and Diagnostic Research  

The findings of this study underscore the potential transformative role of the commercially available Simoa® ALZpath p-Tau 217 assay in AD pathophysiology and diagnostic research. With its high accuracy in identifying abnormal Aβ and tau pathologies, coupled with its ability to track longitudinal changes, plasma p-Tau 217 may hold great promise in the fight against AD. Moreover, the establishment of reference ranges further enhances its potential clinical utility, paving the way for widespread adoption in routine practice. 

Blood-based biomarkers may offer a promising avenue for AD evaluation, providing simple and accessible screening and reducing reliance on CSF and imaging tests. Despite AD’s clinical challenges, especially in early stages, blood biomarkers like p-Tau 217 show promise in revolutionizing AD research, diagnostics, and disease management.  

The increased accessibility of commercially available high-performance assays, such as the Simoa® ALZpath p-Tau 217 assay, holds promise for accelerating the integration of blood biomarkers into clinical settings and offers substantial benefits to the research community. 

Power Neuropathology Research with Quanterix Simoa® Technologies 

Quanterix Simoa® Technologies is raising the bar for diagnostic research by providing ultrasensitivity for biomarker detection from biofluids such as plasma and CSF

Analyses performed on the fully automated Quanterix HD-X platform  can demonstrate excellent precision.Its compatibility with Simoa® assay kits, as well as Homebrew Custom Assay Development, expands research possibilities, making the HD-X a valuable investment for any neuropathology laboratory looking to further their search for biofluid biomarkers that aid diagnosis, disease staging or drug development. 

Explore Our Assays for Neurology 


  1. Ashton NJ, Brum WS, Di Molfetta G, et al. Diagnostic Accuracy of a Plasma Phosphorylated Tau 217 Immunoassay for Alzheimer Disease Pathology. JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319 
  1. Ashton NJ, Puig-Pijoan A, Milà-Alomà M, et al. Plasma and CSF biomarkers in a memory clinic: Head-to-head comparison of phosphorylated tau immunoassays. Alzheimers Dement. 2023;19(5):1913-1924. doi:10.1002/alz.12841 
  1. Janelidze S, Bali D, Ashton NJ, et al. Head-to-head comparison of 10 plasma phospho-tau assays in prodromal Alzheimer’s disease. Brain. 2023;146(4):1592-1601. doi:10.1093/brain/awac333 
  1. Ashton NJ, Janelidze S, Mattsson-Carlgren N, et al. Differential roles of Aβ42/40, p-tau231 and p-tau217 for Alzheimer’s trial selection and disease monitoring. Nat Med. 2022;28(12):2555-2562. doi:10.1038/s41591-022-02074-w 
  1. Jonaitis EM, Janelidze S, Cody KA, et al. Plasma phosphorylated tau 217 in preclinical Alzheimer’s disease. Brain Commun. 2023;5(2):fcad057. Published 2023 Mar 6. doi:10.1093/braincomms/fcad057 
  1. Ashton NJ, Pascoal TA, Karikari TK, et al. Plasma p-tau231: a new biomarker for incipient Alzheimer’s disease pathology. Acta Neuropathol. 2021;141(5):709-724. doi:10.1007/s00401-021-02275-6 
  1. Jani D, Allinson J, Berisha F, et al. Recommendations for Use and Fit-for-Purpose Validation of Biomarker Multiplex Ligand Binding Assays in Drug Development. AAPS J. 2016;18(1):1-14. doi:10.1208/s12248-015-9820-y