Our newest research-advisor Prof. Randall J. Bateman, MD.
ALZpath pTau217 Assay
Pat & Dennis Bender Early Dementia Diagnosis & Prognosis Fund
J. Dennis Bender
Office, Home & Cell Phone: 859-391-5226
5726 La Jolla Blvd. – Suite 311
La Jolla, CA 92037-7345
&
Office - 100 Riverside Pl. - Suite 303
Covington, KY 41011-5711
We support the development of improved diagnostic methods for the early detection and diagnosis of MCI, Alzheimer’s, vascular and other dementias, their likely prognosis, and best treatment options. We focus on the development of Bayesian-based medical-decision-support systems, comparative-effectiveness research, and the better utilization of these for the above. (After incorporating in KY as a 501(c)(3) in 2002, we dissolved that entity in favor of a simplified form of two entirely self-financed, private philanthropies utilizing a Vanguard Charitable Trust for making $100K annual-research-grants for early-dementia-detection and its correct differential-diagnosis and likely-prognosis. They will continue on, after I am long gone, either mentally or physically with annual $750,000 grants. Scripps Foundation, plus Profs. Randall Bateman & James Brewer, will be our fund’s research grant advisors, KMK Law is our legal advisor and David J. Bender is my Estate Rep. (See: https://www.alz.org/alzheimers-dementia/research_progress/earlier-diagnosis)
www.JDBender.com – EMS/eVTOL & Educational Experimental Aviation Fund (Vanguard Charitable Trust)
www.JDBender.org – Dementia Diagnosis Fund (Vanguard Charitable Trust)
January 22, 2024
Cells in an Alzheimer's affected brain, with abnormal levels of the beta-amyloid protein clumping together to form plaques, brown, that collect between neurons and disrupt cell function. Abnormal collections of the tau-protein accumulate and form tangles, blue, within neurons, harming synaptic communication between nerve-cells. (Pat & I on a visit to the University of Gothenburg in Sweden on our Scandinavian vacation.) [National Institute on Aging, NIH via AP]
“A robust and accurate blood-based biomarker would enable a more-comprehensive-assessment of cognitive-impairment in settings where advanced-testing is limited. Therefore, use of a blood-biomarker is intended to enhance an early and precise AD-diagnosis, leading to improved patient management and, ultimately, timely access to disease-modifying therapies. . .
Our findings demonstrate the substantial reduction of confirmatory-testing, by approximately 80%, by implementing a 3-range-approach for Aβ-positivity based on plasma-p-tau217. 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 anti-amyloid-immunotherapies. . . Following the pTau217-level-over-time, we can better understand how various therapies and lifestyle-changes are working to keep-Alzheimer’s-under-better-control. . . When they tested a participant’s blood-sample with the p-tau217-immunoassay, the blood-test showed similar results and accuracies in identifying abnormal-beta-amyloid-and-tau as the results from the participant’s spinal-tap or brain-scan.”
More popular-press coverage of ALZPath’s pTau-217 blood-test that we’ve been discussing, plus speaking directly with its developers over the past year. It appears to be the most-promising of a number of these new blood-based-tests, such as AD-Detect and C2N’s. Which of these may be the better option, in which situations, remains to be established, but this is a major-step in that direction.
Their “findings demonstrate high-accuracy in identifying abnormal-Aβ-and-tau-pathologies, comparable with CSF-measures and superior to brain-atrophy-assessments. A 3-range-approach demonstrated high negative- and positive-concordance with Aβ-status, with approximately 20% of individuals in an intermediate-zone that would require confirmatory-CSF-or-PET, as previously-proposed. Longitudinally, this assay exhibited increases solely in individuals with Aβ-pathology-at-baseline, and those with both-elevated-Aβ-and-tau-pathologies demonstrated a greater-rate-of-annual-increase.
Plasma-biomarkers have emerged as important tools for AD-evaluation. Their specificity to underlying-pathology offers great-potential-for-rapid-screening, reducing the dependence on advanced confirmatory-tests. A clinical-AD-diagnosis often lacks sensitivity and specificity, resulting in many individuals with MCI (40%-60%) or dementia (20%-30%) who exhibit-typical-AD-symptoms-lacking-Aβ-pathology.
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. Thus, blood-biomarkers are set to revolutionize-clinical-care by providing-objective-biomarker-based-information. As anti-Aβ-trials move toward targeting a preclinical-population with lower-prevalence of Aβ-abnormalities, a cost-effective screening strategy becomes paramount. In previous studies, targeting-p-tau217-in-blood has yielded the best results as a diagnostic and prognostic tool that tracks-longitudinal-change.” [Yet another delay in departing for La Jolla.]
New Blood-Test That Screens for Alzheimer's May be a Step-Closer to Reality, Study Suggests
Jacqueline Howard – CNN - Jan. 22, 2024
Testing a person’s blood for a type of protein called phosphorylated-tau, or p-tau, could be used to screen-for-Alzheimer’s-disease with “high-accuracy,” even before symptoms begin to show, a new study suggests.
The study involved testing-blood for a key biomarker of Alzheimer’s called p-tau217, which increases at the same time as other damaging proteins — beta-amyloid and tau — build-up in the brains of people with the disease. Currently, to identify the buildup of beta-amyloid and tau in the brain, patients undergo a brain-scan or spinal-tap, which often can be inaccessible and costly.
But this simple-blood-test was found to be up-to-96%-accurate in identifying elevated levels of beta-amyloid and up to 97%-accurate in identifying tau, according to the study published in the journal JAMA Neurology.
“What was impressive with these results is that the blood-test was just as accurate as advanced-testing like cerebrospinal-fluid-tests and brain-scans at showing Alzheimer’s-disease pathology in the brain,” Nicholas Ashton, a Professor of Neurochemistry at the University of Gothenburg in Sweden and one of the study’s lead authors, said in an email.
The study findings came as no surprise to Ashton, who added that the scientific community has known for several years that using blood-tests to measure tau or other biomarkers has the potential to assess Alzheimer’s-disease-risk.
“Now we are close to these tests being prime-time and this study shows that,” he said. Alzheimer’s-disease, a brain disorder that affects memory and thinking skills, is the most-common type of dementia, according to the National Institutes of Health in the United States.
Last year, a blood-test for assessing beta-amyloid-protein was made available for consumer purchase in the United States, called AD-Detect, to help people with mild-cognitive-impairment identify-their-risk-of-developing-Alzheimer’s-disease. Some researchers have raised doubts about the science behind the test. Quest Diagnostics, the Company behind the test, has stressed that it is not meant to diagnose Alzheimer’s, but says it helps assess-a-person’s-risk-of-developing-the-disease.
The test used in the new study, called the ALZpath-pTau217-assay, is a commercially-available tool developed by the company ALZpath, which provided materials for the study at no cost. The test is currently available for research use only, but Ashton said it is expected to be available for clinical-use soon.
“This is an instrumental finding in blood-based-biomarkers for Alzheimer’s, paving the way for the clinical-use of the ALZpath-pTau-217-assay,” Professors Kaj Blennow and Henrik Zetterberg from the University of Gothenburg, co-authors of the study, said in a press-release. “This robust assay is already used in multiple labs around the globe.”
ALZpath estimates the price of the test could be between US$200 and US$500.
“A robust and accurate blood-based biomarker would enable a more-comprehensive-assessment of cognitive-impairment in settings where advanced testing is limited,” the researchers wrote in their study. “Therefore, use of a blood-biomarker is intended to enhance an early and precise AD diagnosis, leading to improved patient management and, ultimately, timely access to disease-modifying therapies.”
For instance, the test demonstrated “high-accuracy” in identifying-tau-pathology within people who tested-positive for beta-amyloid, according to the study. That may help guide treatment decisions in patients considering therapies that target beta amyloid, such as Leqembi and Aduhelm, since they may be less-effective in patients with advanced-tau-pathology, the researchers wrote.
“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 anti-amyloid immunotherapies,” the researchers wrote.
Blood-test ‘Definitive’ in 80% of Participants
The study included data on 786 people, who had an average-age-of-66 and had brain-scans and spinal-taps completed, as well as blood-samples collected. The data and those samples came from the Translational Biomarkers in Aging and Dementia, Wisconsin Registry for Alzheimer’s Prevention and Sant Pau Initiative on Neurodegeneration.
Some of the participants showed-signs-of-cognitive-decline while undergoing the data-collection but others did not. The researchers, from institutions in Sweden, the United States and other countries, analyzed the participants’ data from February-to-June of last-year.
The researchers found that when they tested a participant’s blood-sample with the p-tau217-immunoassay, the blood-test showed similar results and accuracies in identifying abnormal-beta-amyloid-and-tau as the results from the participant’s spinal-tap or brain-scan.
Only about 20% of the study participants had blood-test-results that, in a clinical-setting, would have required-further-testing with imaging or a spinal-tap due to being unclear.
“This is a significant reduction in costly and high-demand examinations,” Ashton said in the email. Therefore, based on the study findings, “we think that a blood-test and clinical-examination can have definitive-decision in 80%” of those who are being investigated for early-signs-of-dementia.
Yet even though the blood-test in this study was found to be highly-accurate in predicting whether someone has key-characteristics-of-Alzheimer’s-disease in their brain, not everyone with those characteristics will go on to develop the disease.
Also, the p-tau-test is specific for Alzheimer’s-disease, so if someone tests-negative but is showing signs-of-cognitive-impairment, this test could not determine other possible causes of their symptoms, such as vascular-dementia or Lewy-body-dementia.
“A blood-test being negative speeds-up the investigation for other causes of the symptoms and this is just as important,” Ashton said.
Overall, a blood-test-for-Alzheimer’s-disease, such as the one described in the new study, can be used to help diagnose both a person experiencing early-memory-loss, as well as before a patient shows signs or symptoms of the disease, because changes in the brain can occur about-20-years-before the onset-of-overt-symptoms, said Preventive Neurologist Dr. Richard Isaacson, Director of Research at the Institute for Neurodegenerative Diseases in Florida, who was not involved in the study.
“This is actually the test that has, at this time, among the best available evidence for being one single test for Alzheimer’s,” Isaacson said about the study’s findings. “This study takes us one really powerful step closer to having that test, and the beauty of this study is it also looked at people before they had symptoms.”
Signs and symptoms of Alzheimer’s-disease can vary from one person to another, but often memory-problems are the first signs of the disease, such as losing-track-of-dates, getting-lost, misplacing-things or having-difficulty-completing-tasks, such as bathing, reading or writing.
Isaacson, who has researched blood-biomarkers in people with no or minimal-cognitive-complaints, likened testing-blood-samples for signs of Alzheimer’s-disease to how people undergo routine blood-tests for high-cholesterol.
“People get cholesterol-tests before they have a heart attack. People get cholesterol tests before they have a stroke. To me, this type of test will eventually be best served in people before they start to have cognitive symptoms,” Isaacson said. And “just like cholesterol-tests, by following the pTau217-level-over-time, we can better understand how various therapies and lifestyle-changes are working to keep-Alzheimer’s-under-better-control.”
A Way to Help ‘Democratize Access’ Testing for Alzheimer’s before someone has symptoms “leaves a lot of time” for that person to make brain-healthy choices and to talk to their doctor about their individual risk factors, Isaacson said, adding that a blood-based-test also can be more-cost-effective than performing brain-scans or other methods of testing.
“PET-scans have radiation and can cost over US$5,000. Spinal-taps are great because you get detailed information, but not everyone wants one and it is expensive and not-covered-by-insurance. These blood-tests are generally more-reasonably-priced,” Isaacson said.
“Having a blood-test like this can also help democratize access for people and just make it easier for our healthcare system to more-proactively-manage the tsunami of dementia-risk that our society is facing,” he said. “This is the key to unlock-the-door into the field of Alzheimer’s-prevention and preventive-neurology.”
More than 6-million people in the United States are living with dementia caused by Alzheimer’s-disease, according to the Alzheimer’s Association, and the number of people affected is projected to double in the next two-decades, rising to some 13-million in 2050.
In the future, adults-older-than-50 may be recommended-to-undergo-routine-blood-tests-for-Alzheimer’s-disease, said David Curtis, Honorary Professor at the University College London, who was not involved in the new study.
“When effective-treatments to prevent-the-progression-of-Alzheimer’s-disease become available it will be essential to be able to identify people who are a- high-risk before-they-begin-to-deteriorate. This study shows that a simple-blood-test might be able to do this by measuring-levels-of-tau-protein-in-the-blood which has been phosphorylated in a specific-way. This could potentially have huge-implications,” Curtis said in a statement distributed by the UK-based Science Media Centre.
“Everybody-over-50 could be routinely-screened-every-few-years, in much the same way as they are now screened for high-cholesterol. It is possible that currently available treatments for Alzheimer’s-disease would work better in those diagnosed early in this way,” he said. “However, I think the real hope is that better-treatments can also be developed. The combination of a simple-screening-test with an effective-treatment-for-Alzheimer’s-disease would have a dramatic-impact for individuals and for society.”
Original Investigation - January 22, 2024
Diagnostic Accuracy of a Plasma Phosphorylated-Tau-217-Immunoassay for Alzheimer-Disease-Pathology
Nicholas J. Ashton, PhD1,2,3,4; Wagner S. Brum1,5; Guglielmo Di Molfetta, MSc1; et alAndrea L. Benedet, PhD1; Burak Arslan, MD1; Erin Jonaitis, PhD6,7,8; Rebecca E. Langhough, PhD6,7,8; Karly Cody, PhD7; Rachael Wilson, PhD7,8; Cynthia M. Carlsson, PhD6,7,8,9; Eugeen Vanmechelen, PhD10; Laia Montoliu-Gaya, PhD1; Juan Lantero-Rodriguez, PhD1; Nesrine Rahmouni, MSc11,12; Cecile Tissot, PhD11,12; Jenna Stevenson, PhD11,12; Stijn Servaes, PhD11,12; Joseph Therriault, PhD11,12; Tharick Pascoal, MD, PhD13,14; Alberto Lleó, MD, PhD15,16; Daniel Alcolea, MD, PhD15,16; Juan Fortea, MD, PhD15,16; Pedro Rosa-Neto, MD, PhD11,12; Sterling Johnson, MD, PhD6,7; Andreas Jeromin, PhD17; Kaj Blennow, MD, PhD1,18; Henrik Zetterberg, MD, PhD1,7,18,19,20,21
Author Affiliations Article Information
JAMA Neurol. Published online January 22, 2024. doi:10.1001/jamaneurol.2023.5319
Key Points
Question What are the capabilities of a commercially available plasma phosphorylated-tau 217 (p-tau217) immunoassay to identify Alzheimer-disease pathophysiology?
Findings This cohort study found that the p-tau217 immunoassay showed similar accuracies to cerebrospinal-fluid biomarkers in identifying abnormal amyloid β (Aβ) and tau pathologies. A 3-range reference for detecting abnormal Aβ pathology was consistent across 3 cohorts; over 8 years, the largest change of p-tau217 was in individuals positive for both Aβ and tau.
Meaning The wider availability of high-performing assays may expedite the use of blood-biomarkers in clinical settings and benefit the research community.
Abstract
Importance Phosphorylated-tau (p-tau) is a specific blood-biomarker for Alzheimer-disease (AD) pathology, with p-tau217 considered to have the most utility. However, 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.
Objective 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.
Design, Setting, and Participants 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.
Exposures 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).
Main Outcomes and Measures Accuracy of plasma-p-tau217 in detecting abnormal amyloid and tau pathology, longitudinal p-tau217 change according to baseline pathology status.
Results 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 signal. 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.
Conclusions and Relevance 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.
Introduction In Alzheimer-disease (AD), blood-biomarkers have emerged as scalable-tools for clinical-evaluation, trial-recruitment, and disease-monitoring.1 Their anticipated implementation aims to substantially reduce the reliance on cerebrospinal-fluid (CSF) or positron-emission-tomography (PET) scans in specialized centers.2 Moreover, a robust and accurate blood-based biomarker would enable a more comprehensive assessment of cognitive impairment in settings where advanced testing is limited. Therefore, use of a blood-biomarker is intended to enhance an early and precise AD diagnosis, leading to improved-patient-management and, ultimately, timely-access to disease-modifying-therapies.
Phosphorylated-tau (p-tau) is the leading blood-biomarker-candidate, demonstrating superior diagnostic-accuracy and disease-specificity compared with other candidates.3,4 The amyloid-β-42/40 (Aβ42/40)-ratio, a validated CSF biomarker,5 has limitations in blood6,7 and lacks the robustness required for routine-clinical-testing.8,9 In contrast, high-performing p-tau-blood-test results exhibit a substantial increase in patients with AD,10 occurring concurrently with extracellular-Aβ-plaque deposition, an AD-hallmark-feature. This relationship is observed across the AD-continuum, including the asymptomatic-phase in sporadic and genetic-forms of AD.11-14 Yet certain p-tau-species, but not all, are also associated with neurofibrillary-tangle-pathology, the secondary-AD-pathological-hallmark.15-17 Thus, p-tau is regarded as the primary-blood-biomarker for AD-pathology throughout all stages of the disease.
Among proposed blood-tau-biomarkers,18-21 phosphorylated-tau at threonine-217 (p-tau217) has consistently shown high-performance in differentiating AD from other neurodegenerative-disorders10,22 and in detecting-AD-pathology in patients with mild-cognitive-impairment (MCI).22 Notably, p-tau217 exhibits larger-fold-changes compared with p-tau181 and p-tau231,10 often achieving high-discrimination, with areas under the curve (AUC) exceeding 90%.19,23 Additionally, p-tau217 demonstrates a unique-longitudinal-trajectory, showing increases associated with worsening-brain-atrophy and declining-cognitive-performance in individuals with elevated-Aβ-pathology.24,25
With the imminent implementation of anti-Aβ-therapies in dementia-management, validated blood-biomarkers are urgently needed to guide-timely-treatment-decisions. While plasma-p-tau217 has shown promise as a diagnostic-tool-for-AD, its widespread evaluation has been hindered by limited-availability of commercial-assays. This study aims to address this gap by assessing the utility of ALZpath-pTau217, a commercially-available immunoassay, to highlight the presence of AD pathology. In addition, we aim to report reference-ranges of the plasma-p-tau217 that correspond to abnormal amyloid PET and CSF measures.
Methods This study included participants from 3 observational cohorts: the Translational Biomarkers in Aging and Dementia (TRIAD), Wisconsin Registry for Alzheimer’s Prevention (WRAP), and Sant Pau Initiative on Neurodegeneration (SPIN). Participants gave written or verbal informed consent, and the studies were approved by the relevant ethics boards (eMethods in Supplement 1). The present study followed the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting guidelines.
TRIAD included 268 participants who had no cognitive impairment (134 individuals [50%]), MCI (63 [23.5%]), AD-dementia (46 [17.2%]), and non-AD-dementia (24 [9.0%]). The WRAP study26 included data on 323 participants, predominantly without cognitive impairment at the first plasma sample collection (no impairment, 309 [95.6%]; MCI, 12 [3.7%]; AD-dementia, 2 [0.6%]). The SPIN cohort27 included 195 participants: controls without cognitive impairment (82 [42.1%]), individuals with MCI due to AD (72 [36.7%]), and individuals with AD-dementia (41 [21.0%]). Diagnosis was based on internationally recognized clinical criteria, and control participants had normal cognitive scores on standard neuropsychological evaluations. A subset of patients with longitudinal follow-up consisted of 392 participants from TRIAD and WRAP defined by PET biomarkers (eTable 1 in Supplement 1). These included participants classified into 3 groups: amyloid- and tau-negative (A−T−; n = 297), amyloid-positive and tau-negative (A+T−; n = 66), and amyloid-positive and tau-positive (A+T+; n = 29). In WRAP, the median number of samples collected per patient was 3 over a mean (SD) of 5.22 (1.41) years. In TRIAD, median samples per patient was 2, collected over a mean of 1.90 (0.61) years.
Imaging, CSF, and Plasma Biomarkers Detailed imaging methods for TRIAD, WRAP, and SPIN are found in the eMethods in Supplement 1. In TRIAD, Aβ and tau PET were determined by [18F]-AZD469428 and [18F]-MK6240,29 respectively. In WRAP, PET measures were determined by [11C]-PiB30 and [18F]-MK6240.31,32 In SPIN, Aβ PET was determined by [18F]-florbetapir or [18F]-flutemetamol in a smaller subset of participants, with CSF Aβ42/40 used to define A status for most participants as described below. Tau PET was not available for the SPIN cohort, and T was defined by CSF p-tau181. Aβ-PET positivity was standardized across cohorts as a centiloid value greater than 24 (standardized uptake value ratio [SUVR] >1.55 for [18F]-AZD469433 or distribution volume ratio >1.2 for [11C]-PiB), [that we helped to develop back in early 2000s at the U. of Pittsburgh.] Tau-positivity with [18F]-MK6240 was defined as meta-temporal region of interest SUVR greater than 1.24 for TRIAD34 and SUVR greater than 1.3 in WRAP.
CSF sample collection procedures were similar across cohorts and are described in the eMethods in Supplement 1. In TRIAD and SPIN, Lumipulse G1200 or G600II was used to quantify CSF Aβ42, Aβ40, and p-tau181.35,36 Additionally, CSF p-tau217 was quantified by an in-house single-molecule array (Simoa) developed at the University of Gothenburg.33 A novel Simoa for CSF p-tau205 was measured in TRIAD only. For WRAP, CSF Aβ42, Aβ40, and p-tau181 were measured using the Roche NeuroToolKit.37
Plasma samples from TRIAD, WRAP, and SPIN were analyzed at the Department of Psychiatry and Neurochemistry, University of Gothenburg. Plasma Aβ42/40, glial fibrillary acidic protein (GFAP), and neurofilament light chain (NfL) were quantified using the commercial Neurology 4-plex E kit (103670; Quanterix). Plasma p-tau231 and p-tau181 were analyzed using in-house Simoa assays developed at the University of Gothenburg,18,38 except in WRAP where plasma p-tau181 was quantified by the commercial Advantage kit version 2.1 (104111; Quanterix).24
Novel p-Tau217 Assay The commercial ALZpath-pTau217 assay for p-tau217 uses a proprietary monoclonal-p-tau217 specific capture antibody, an N-terminal-detector-antibody, and a peptide-calibrator. It has been validated as a fit-for-purpose-assay38 with a limit-of-detection of 0.0052 to 0.0074 pg/mL, a functional lower limit of quantification of 0.06 pg/mL, and a dynamic range of 0.007 to 30 pg/mL. The spike recovery for the endogenous analyte was 80%, and intrarun and interrun precision was 0.5% to 13% and 9.2% to 15.7%, respectively. Here, the assay demonstrated good-repeatability (4%-8.7%) and intermediate-precision (3.5%-10.7%) as shown in eTable 2 in Supplement 1.
Statistical Analysis Between-group-comparisons were conducted using linear-models, adjusting for age and sex. Determining Aβ-PET and tau-PET positivity and other outcomes was done using receiver-operating-characteristics AUC and compared with those of other established biomarkers with the DeLong-test. Correlations were always evaluated using Spearman-ρ. A binary-reference-point for Aβ-PET-positivity was derived based on the Youden-index.
Alternatively, a 3-range strategy comprised a lower-reference-point to rule-out-AD (95%-sensitivity) and a higher-reference-point to rule-in-AD (95%-specificity). In both strategies, we evaluated the concordance of a negative p-tau217 result with Aβ-PET negativity (negative-percent-agreement), and the concordance of a positive plasma-p-tau217 with Aβ-PET positivity (positive-percent-agreement), as well as the overall percent agreement. In the latter strategy, individuals with p-tau217-levels between the reference-point were classified as intermediate-risk and would constitute the population referred to confirmatory-testing.39
We evaluated the longitudinal-trajectories of plasma-p-tau217 in participants with no cognitive impairment and those with MCI according to their amyloid (A) and tau (T) status. We used linear-mixed-effects-models with plasma-p-tau217 as the response-variable, including as predictors time (since first plasma collection), AT-status, age-at-first-plasma-collection, years-of-education, sex, and cognitive-status-at-first-visit, as well as an interaction between AT status and time. The model contained random-intercepts and random-slopes for each participant, and time was modeled as a continuous-variable. Post-hoc-pairwise-contrasts were conducted to compare the slopes for group×time-interactions.
All analyses were performed using R version 4.2.2 (R Project for Statistical Computing), with a 2-sided-α of .05. No adjustments for multiple-comparisons were performed.40 Reported results include 95%-confidence-intervals when applicable.
Results - Participant Characteristics A total of 786 participants (mean [SD] age, 66.3 [9.7] years; 504 females [64.1%], 282 males [35.9%]) were included in the study. The TRIAD subsample included 268 participants (69.4 [7.8] years; 167 females [62.3%], 101 males [37.7%]). The WRAP cohort included 323 participants (65.3 [6.9] years; 217 females [67.2%], 106 males [32.8%]), predominantly without cognitive impairment. The SPIN cohort included 195 participants (63.5 [13.8] years; 120 females [61.5%], 75 males [38.5%]). All participants had confirmatory amyloid status (TRIAD and WRAP: Aβ PET; SPIN: CSF Aβ42/Aβ40), and the majority (716 [91.1%]) also had information on tau status (TRIAD and WRAP: tau PET; SPIN: CSF p-tau181), as described in Table 1 alongside demographic and clinical information for all cross-sectional analyses. eTable 2 in Supplement 1 describes the TRIAD and WRAP longitudinal subsets.
p-Tau217 Levels by Amyloid and Tau Status When stratified by AT status, regardless of clinical diagnosis, plasma-p-tau217 significantly increased in a stepwise manner in all cohorts (Figure 1), with highest levels in the A+T+ group. Mean p-tau217 concentrations for A−T− (mean [SD] TRIAD, 0.26 [0.13] pg/mL; WRAP, 0.35 [0.15] pg/mL; SPIN, 0.32 [0.11] pg/mL), A+T− (TRIAD, 0.75 [0.63] pg/mL; WRAP, 0.72 [0.30] pg/mL; SPIN, 0.91 [0.47] pg/mL), and A+T+ (TRIAD, 1.48 [0.65] pg/mL; WRAP, 1.41 [0.70] pg/mL; SPIN, 1.50 [0.70] pg/mL) were remarkably similar across all 3 cohorts. This was also observed when stratifying by amyloid status alone (A−, TRIAD, 0.28 [0.21] pg/mL; WRAP, 0.35 [0.14] pg/mL; SPIN, 0.38 [0.29] pg/mL; and A+, TRIAD, 1.08 [0.72] pg/mL, WRAP, 0.94 [0.54] pg/mL, SPIN, 1.43 [0.70] pg/mL) (eFigure 1 in Supplement 1).
Accuracy in Discriminating Abnormal Aβ and Tau Pathologies Plasma-p-tau217 demonstrated high-accuracy in predicting abnormal Aβ-PET signal (centiloid >24) in TRIAD (AUC, 0.92; 95% CI, 0.92-0.96) and WRAP (AUC, 0.93; 95% CI, 0.90-0.97) (Figure 2A). In SPIN, p-tau217 also had high-accuracy in predicting abnormal CSF Aβ42/40 (AUC, 0.96; 95% CI, 0.92-0.99) (Figure 2A). There was equally high-accuracy when Aβ-PET status was determined by visual-read (eFigure 2 in Supplement 1). Further, p-tau217 sustained high-accuracy when Aβ-PET-status was defined by differing centiloid-values (e.g., centiloid >12 and centiloid >37) in TRIAD and WRAP participants (eFigure 3 in Supplement 1).
Plasma-p-tau217 also exhibited high-accuracy for predicting abnormal tau in TRIAD (AUC, 0.95; 95% CI, 0.92-0.97) and WRAP (AUC, 0.93; 95% CI, 0.84-0.98) (Figure 2B). In SPIN, p-tau217 had high-accuracy for abnormal CSF p-tau181 (AUC, 0.97; 95% CI, 0.94-0.99). Promisingly, p-tau217 could identify abnormal tau PET signal among amyloid-positive participants (A+T− vs A+T+) in TRIAD (AUC, 0.87; 95% CI, 0.81-0.93) and WRAP (AUC, 0.90; 95% CI, 0.85-0.95) (Figure 2C). Moreover, we observed a gradual increase of plasma-p-tau217 across tau-PET–defined Braak-stages in TRIAD (eFigure 4 and eTable 3 in Supplement 1).
Comparing p-Tau217 With Imaging and CSF-biomarkers in Identifying AD Pathology Next, we compared the performance of plasma-p-tau217 to CSF and imaging modalities for predicting abnormal Aβ PET and tau PET. This analysis included the maximum number of participants within each biomarker-modality. In WRAP, in determining abnormal Aβ PET, plasma-p-tau217 outperformed hippocampal atrophy (AUC, 0.52; 95% CI, 0.44-0.60; P < .001), tau PET (AUC, 0.72; 95% CI, 0.64-0.80; P < .001), and CSF p-tau181 (AUC, 0.75; 95% CI, 0.66-0.84; P < .001) but did not differ significantly from CSF Aβ42/40 or CSF p-tau181/Aβ42 (eFigure 5A in Supplement 1). Similar findings were observed in TRIAD, where plasma-p-tau217 outperformed hippocampal atrophy (AUC, 0.70; 95% CI, 0.63-0.76; P < .001) and tau PET (AUC, 0.86; 95% CI, 0.82-0.91; P = .05) for detecting abnormal Aβ pathology but did not significantly differ from various CSF-biomarkers (eFigure 5B in Supplement 1). In SPIN, plasma-p-tau217 outperformed hippocampal-volume (AUC, 0.89; 95% CI, 0.83-0.95; P = .04) and was comparable with CSF-biomarkers (eFigure 5C in Supplement 1).
In predicting abnormal-tau-PET-burden (eFigure 5D-E in Supplement 1), plasma-p-tau217 significantly outperformed hippocampal-volume (WRAP AUC, 0.65; 95% CI, 0.50-0.81; P = .01; TRIAD AUC, 0.83; 95% CI, 0.76-0.89; P = .01; SPIN AUC, 0.91; 95% CI, 0.86-0.96, P = .049). Plasma-p-tau217 significantly outperformed CSF p-tau181 in WRAP (AUC, 0.69; 95% CI, 0.66-0.84; P = .02) but not TRIAD. Plasma-p-tau217 outperformed Aβ PET in TRIAD (AUC, 0.90; 95% CI, 0.86-0.95; P = .04), while in WRAP they were comparable (AUC, 0.96; 95% CI, 0.93-0.99; P = .35). Plasma-p-tau217 showed comparable performance with other measures, except for CSF p-tau217 in SPIN.
Additionally, we conducted comparisons in subsets only including participants with all modalities (WRAP: n = 131; TRIAD: n = 106; SPIN: n = 41), finding no marked differences (eFigure 6 in Supplement 1). Plasma-p-tau217 also discriminated A+T+ from A+T− individuals comparably with CSF and imaging biomarkers (eFigure 7 in Supplement 1).
Comparing p-Tau217 With Other Plasma Biomarkers Plasma-p-tau217-alone or p-tau217-plus-demographic-variables (age, sex, and APO- status) outperformed all other plasma-biomarkers (p-tau181, p-tau231, Aβ42/40, GFAP, and NfL), and their optimal-combinations, for predicting both amyloid and tau status in all cohorts (eTables 4 and 5 and eFigure 7 in Supplement 1). A minimal-improvement in model-metrics of goodness-of-fit (Akaike-information-criterion) was observed in p-tau217 plus demographic-data but not in discriminatory-performance. The correlations of plasma-p-tau217 with Aβ PET, tau PET, and CSF p-tau217 are shown in eFigures 9 and 10 in Supplement 1.
Reference Ranges for Plasma-p-tau217 With Abnormal Aβ and Tau Pathologies We first derived a binary-reference-point for Aβ-positivity using the Youden-index, derived in WRAP (>0.42 pg/mL) (Table 2 and eFigure 11 in Supplement 1). This reference-point was cross-validated in TRIAD (Aβ-positivity based on PET) and SPIN (Aβ-positivity based on CSF Aβ42/40). We next applied a 3-range approach,41 creating lower (95%-sensitivity, <0.4 pg/mL) and upper (95%-specificity, >0.63 pg/mL) reference-points in WRAP (Table 2 and eFigure 11 in Supplement 1). This approach improved the positive-percent-agreement (TRIAD: 97.7%; SPIN: 95.3%) while maintaining a similar negative-percent-agreement. The “intermediate”-zone (p-tau217 levels 0.4-0.63 pg/mL), which could in practice be referred to confirmatory-testing with CSF or PET, was largest in WRAP (22.9%), as expected because of lower-Aβ-positivity-prevalence, and smaller in TRIAD (15.8%) and SPIN (13.0%). A binary-reference-point for tau-positivity is demonstrated in eTable 6 in Supplement 1.
Longitudinal-Changes in Plasma-p-tau217-Levels In up to 8-years of longitudinal-sampling in WRAP (mean [SD], 5.22 [1.41] years), the A+T+ group demonstrated a significantly-higher annual increase rate in plasma-p-tau217 levels compared with the A−T− group (β estimate, 0.12; 95% CI, 0.10-0.13; P < .001). The A+T− group also demonstrated a significantly higher annual rate of change in plasma-p-tau217 compared with A−T− (β estimate, 0.04; 95% CI, 0.02-0.05; P < .001). Slope comparisons showed the A+T+ group to have a significantly higher rate compared with the A+T− group (β estimate, 0.08; 95% CI, 0.06-0.09; P < .001) (Figure 3A). In TRIAD, similar results were observed, even with a shorter follow-up (mean [SD], 1.90 [0.61] years) (Figure 3B).
Discussion In 3 independent cohorts, this study presents the performance of a commercially-available plasma-assay targeting-p-tau217. Our findings demonstrate high-accuracy in identifying abnormal-Aβ-and-tau-pathologies, comparable with CSF-measures and superior to brain-atrophy-assessments. A 3-range-approach demonstrated high negative- and positive-concordance with Aβ-status, with approximately 20% of individuals in an intermediate-zone that would require confirmatory-CSF-or-PET, as previously-proposed.41 Longitudinally, this assay exhibited increases solely in individuals with Aβ-pathology-at-baseline, and those with both-elevated-Aβ-and-tau-pathologies demonstrated a greater-rate-of-annual-increase.
Plasma-biomarkers have emerged as important tools for AD-evaluation. Their specificity to underlying-pathology offers great-potential-for-rapid-screening, reducing the dependence on advanced confirmatory-tests. A clinical-AD-diagnosis often lacks sensitivity and specificity, resulting in many individuals with MCI (40%-60%) or dementia (20%-30%) who exhibit-typical-AD-symptoms-lacking-Aβ-pathology.1
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.1 Thus, blood-biomarkers are set to revolutionize-clinical-care by providing-objective-biomarker-based-information. As anti-Aβ-trials move toward targeting a preclinical population with lower prevalence of Aβ abnormalities,42 a cost-effective screening strategy becomes paramount. In previous studies, targeting p-tau217-in-blood has yielded the best results as a diagnostic and prognostic tool that tracks-longitudinal-change.
There has been limited access to immunoassays-targeting-p-tau217 for broader-evaluation. This study evaluates a commercially-available-assay for p-tau217 that exhibits similar advantageous features to those previously reported. Consistent with Palmqvist et al,19 this assay outperformed magnetic-resonance-imaging and showed comparable-performance with CSF-biomarkers in detecting Aβ-PET-positivity and tau-PET-positivity.43 Further, significant superiority to other plasma-p-tau-epitopes, Aβ42/40, NfL, and GFAP and their optimal-combinations was shown. When combined with APOE-status and age, only modest improvements in diagnostic accuracy were observed, whereas other plasma biomarkers relied more-heavily on these variables for their performance.
Notably, the assay demonstrated high-accuracy in identifying-tau-pathology within Aβ-positive-individuals. This is particularly important as anti-amyloid-therapies may be less-effective in patients with advanced-tau-pathology.44,45 Our findings suggest that p-tau217 has the potential to identify elevated tau-PET-uptake and promising-utility in early-AD-trials. Our study did not define elevated-tau in the same manner as the TRAILBLAZER-trials but warrants further studies applying p-tau217 to intermediate-tau-trial-inclusion-designs.45
Integrating-blood-biomarkers into diagnostic-workflows remains challenging despite their promise. Therefore, this study also aimed to establish-reference-points based on abnormal-Aβ-pathology. The study evaluated a 3-range-approach as recommended by Alzheimer’s Association guidelines39 and recently proposed by Brum et al,41 which suggests confirmatory-testing for patients with uncertain-plasma-p-tau217-results. Evaluating this approach using a commercial-immunoassay showed high-negative and positive predictive-accuracy-at-screening, indicating only 12%-to-23% of individuals warranted advanced testing, depending on the clinical-stage.
However, we acknowledge that the cohorts used in this study may not fully represent real-world-clinical-settings. Importantly, the reported negative and positive predictive accuracy of these reference ranges can vary based on the prevalence of the outcome in the target population. Lower positive-percent-agreements are expected in settings with lower-prevalence,46 as observed in the preclinical-WRAP-cohort compared with the higher-prevalence seen in TRIAD and SPIN cohorts. Therefore, future studies should prospectively-evaluate plasma-p-tau217 reference-points in memory-clinic-populations with wider-diversity to ensure optimized-implementation, accounting for higher-rates-of-important-comorbidities.47
Limitations This study is not without limitations. First, one-third of our participants were classified as cognitively-impaired, and this may limit our generalizability to the symptomatic-stages of the disease but highlights promise for future preclinical-recruitment. In addition, our results cannot be generalized to all individuals without detailed examination in cohorts with a larger representation of diverse-ethnic-populations. We acknowledge that CSF-p-tau181, utilized as a T-marker in SPIN, is not interchangeable with other methods that more-accurately-reflect neurofibrillary-tangle-pathology.48
Conclusions This study highlights the effectiveness of a commercially-available plasma-p-tau217-assay in identifying-AD-pathology. Our findings demonstrate the substantial reduction of confirmatory-testing, by approximately 80%, by implementing a 3-range-approach for Aβ-positivity based on plasma-p-tau217. 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 anti-amyloid-immunotherapies.
Article Information
Accepted for Publication: November 10, 2023.
Published Online: January 22, 2024. doi:10.1001/jamaneurol.2023.5319
Open Access: This is an open access article distributed under the terms of the CC-BY License. © 2024 Ashton NJ et al. JAMA Neurology.
Corresponding Author: Nicholas J. Ashton, PhD, Institute of Neuroscience and Physiology, Department of Psychiatry and Neurochemistry, Sahlgrenska Academy at Gothenburg University, Mölndal Hospital, Hus V3, 43180 Mölndal, Sweden (
Author Contributions: Dr Ashton had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Dr Ashton and Mr Brum contributed equally as co–first authors.
Concept and design: Ashton, Brum, Benedet, Vanmechelen, Montoliu-Gaya, Servaes, Therriault, Pascoal, Johnson, Blennow, Zetterberg.
Acquisition, analysis, or interpretation of data: Ashton, Brum, Di Molfetta, Benedet, Arslan, Jonaitis, Langhough, Cody, Wilson, Carlsson, Montoliu-Gaya, Lantero-Rodriguez, Rahmouni, Tissot, Stevenson, Therriault, Pascoal, Lleó, Alcolea, Fortea, Rosa-Neto, Johnson, Jeromin, Blennow, Zetterberg.
Drafting of the manuscript: Ashton, Brum, Arslan, Johnson.
Critical review of the manuscript for important intellectual content: Ashton, Brum, Di Molfetta, Benedet, Jonaitis, Langhough, Cody, Wilson, Carlsson, Vanmechelen, Montoliu-Gaya, Lantero-Rodriguez, Rahmouni, Tissot, Stevenson, Servaes, Therriault, Pascoal, Lleó, Alcolea, Fortea, Rosa-Neto, Johnson, Jeromin, Blennow, Zetterberg.
Statistical analysis: Ashton, Brum, Jonaitis, Therriault.
Obtained funding: Tissot, Fortea, Rosa-Neto, Johnson, Zetterberg.
Administrative, technical, or material support: Ashton, Benedet, Jonaitis, Cody, Wilson, Carlsson, Vanmechelen, Montoliu-Gaya, Rahmouni, Tissot, Stevenson, Servaes, Therriault, Lleó, Fortea, Rosa-Neto, Jeromin, Zetterberg.
Supervision: Ashton, Fortea, Blennow.
Conflict of Interest Disclosures: Dr Jonaitis reported grants from National Institutes of Health and tau tracer from Cerveau during the conduct of the study. Dr Langhough reported grants from the National Institutes of Health (NIH) during the conduct of the study. Dr Cody reported grants from NIH during the conduct of the study. Dr Wilson reported grants from University of Wisconsin–Madison during the conduct of the study. Dr Carlsson reported grants from NIH during the conduct of the study. Dr Lleó reported personal fees from Fujirebio-Europe, Roche, Biogen, Lilly, and Nutricia outside the submitted work and having had a patent for markers of synaptopathy in neurodegenerative disease licensed to ADx. Dr Alcolea reported grants from Fondo de Investigaciones Sanitario, Carlos III Health Institute, and Departament de Salut de la Generalitat de Catalunya during the conduct of the study; advisory board services and/or speaker honoraria from Fujirebio-Europe, Roche, Nutricia, Krka Farmacéutica, Grifols, Lilly, Zambon, Esteve, and Neuraxpharm outside the submitted work; and having had a patent for EPI8382175.0 licensed to ADx. Dr Fortea reported grants from Fondo de Investigaciones Sanitario (FIS), Instituto de Salud Carlos III, NIH, and Horizon 2020 (European Commission) during the conduct of the study; personal fees from Roche, Novo Nordisk, Esteve, Biogen, Laboratorios Carnot, LMI, AC Immune, Alzheon, Lundbeck, and Lilly outside the submitted work; and having had a patent issued for WO2019175379 A1, “Markers of synaptopathy in neurodegenerative disease,” with royalties paid. Dr Rosa-Neto reported funding from the Weston Brain Institute, Canadian Institutes of Health Research (MOP-11-51-31, FRN, 152985); salary award from the Fonds de Recherche du Québec–Santé and Colin J. Adair Charitable Foundation; serving on the advisory board for Novo Nordisk, Eisai, and Eli Lilly; and serving as a consultant for Eisai and Cerveau Radiopharmaceuticals. Dr Johnson reported grants from NIH and advisory board fees from ALZpath during the conduct of the study, grants from Cerveau Technologies paid to his institution outside of the submitted work, and advisory board fees from Roche Diagnostics and Prothena outside the submitted work. Dr Jeromin reported equity from ALZpath and having had a patent pending for ALZpath. Dr Blennow reported having served as a consultant and at advisory boards for Acumen, ALZpath, BioArctic, Biogen, Eisai, Lilly, Moleac, Novartis, Ono Pharma, Prothena, Roche Diagnostics, and Siemens Healthineers; having served at data monitoring committees for Julius Clinical and Novartis; having given lectures, produced educational materials, and participated in educational programs for AC Immune, Biogen, Celdara Medical, Eisai, and Roche Diagnostics; and being a co-founder of Brain Biomarker Solutions in Gothenburg AB (BBS), which is a part of the GU Ventures Incubator Program. Dr Zetterberg reported advisory board fees from AbbVie, Acumen, Alector, Alzinova, ALZpath, Annexon, Apellis, Artery Therapeutics, AZTherapies, Cognito Therapeutics, CogRx, Denali, Eisai, Nervgen, Novo Nordisk, Optoceutics, Passage Bio, Pinteon Therapeutics, Prothena, Red Abbey Labs, reMYND, Roche, Samumed, Siemens Healthineers, Triplet Therapeutics, and Wave Scientific; sponsored lecture fees from Cellectricon, Fujirebio, Alzecure, Biogen, and Roche; and being a co-founder and stockholder for Brain Biomarker Solutions in Gothenburg AB outside the submitted work. No other disclosures were reported.
Funding/Support: ALZpath provided the materials for this study at no cost. This work was supported by National Institutes of Health (NIH) grants (1R01AG056850-01A1; R21AG056974 and R01AG061566 to Dr Lleó) and Department de Salut de la Generalitat de Catalunya, Pla Estratègic de Recerca I Innovació en Salut (SLT006/17/00119 to Dr Fortea; SLT002/16/00408 to Dr Lleó; SLT006/17/125 to Dr Alcolea). It was also supported by Horizon 2020–Research and Innovation Framework Programme from the European Union (H2020-SC1-BHC-2018-2020 to Dr Fortea). Drs Lleó, Alcolea, and Fortea were supported by the Fondo de Investigaciones Sanitario, Carlos III Health Institute (PI20/01330 to Dr Lleó, PI18/00435 and INT19/00016 to Dr Alcolea, PI20/01473 to Dr Fortea) and the Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas (CIBERNED) Program 1. Dr Blennow is supported by the Swedish Research Council (2017-00915 and 2022-00732), Swedish Alzheimer Foundation (AF-930351, AF-939721, and AF-968270), Hjärnfonden, Sweden (FO2017-0243 and ALZ2022-0006), Swedish state under the agreement between the Swedish government and the County Councils, ALF-agreement (ALFGBG-715986 and ALFGBG-965240), European Union Joint Program for Neurodegenerative Disorders (JPND2019-466-236), Alzheimer’s Association 2021 Zenith Award (ZEN-21-848495), and Alzheimer’s Association 2022-2025 grant (SG-23-1038904 QC). Dr Zetterberg is a Wallenberg Scholar supported by grants from the Swedish Research Council (2022-01018 and 2019-02397), European Union’s Horizon Europe research and innovation programme (grant agreement 101053962), Swedish State Support for Clinical Research (ALFGBG-71320), Alzheimer Drug Discovery Foundation (201809-2016862), AD Strategic Fund, and Alzheimer’s Association (ADSF-21-831376-C, ADSF-21-831381-C, and ADSF-21-831377-C), Bluefield Project, Olav Thon Foundation, Erling-Persson Family Foundation, Stiftelsen för Gamla Tjänarinnor, Hjärnfonden, Sweden (FO2022-0270), European Union’s Horizon 2020 research and innovation programme (Marie Skłodowska-Curie grant agreement 860197, MIRIADE), European Union Joint Programme–Neurodegenerative Disease Research (JPND2021-00694), National Institute for Health and Care Research University College London Hospitals Biomedical Research Centre, and UK Dementia Research Institute at UCL (UKDRI-1003). The Wisconsin Registry for Alzheimer’s Prevention is supported by NIH grants AG027161 and AG021155.
Role of the Funder/Sponsor: ALZpath reviewed the manuscript before submission. Otherwise, the funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.
Data Sharing Statement: See Supplement 2.
Additional Contributions: We thank Jeroen Vanbrabant, PhD, and Erik Stoops, PhD, from ADx Neuroscience, now Fujirebio, and the accelerator lab at Quanterix, for the initial prototyping of the ALZpath-pTau217 assay.
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{ALZpath-pTau217 Assay}
1