Novel Blood Test Shows High Accuracy in Identifying Alzheimer Disease Pathology

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In a recent study, a new blood test displayed remarkable accuracy in detecting Alzheimer disease pathology, showing its potential as an essential screening tool.

Nicholas Ashton, PhD, associate professor of neurochemistry at University of Gothenburg in Sweden

Nicholas Ashton, PhD

Credit: Research Gate

Newly published in JAMA Neurology, a cohort study showed that a novel and commercially available plasma phosphorylated tau217 (p-tau) immunoassay had high accuracy in identifying Alzheimer disease (AD) pathology.1 These findings suggest that wider availability of high-performing assays is essential for wider evaluation and implementation of AD blood tests in the clinical practice.2

Among 786 patients (mean age, 66.3 [SD, 9.7] years; women, n = 504 [64.1%]; men, n = 282 [35.9%]), investigators observed high accuracy in identifying elevated amyloid β (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 3 selected cohorts. Notably, researchers observed that these accuracies showed similar results to using cerebrospinal fluid (CSF) biomarkers, Aβ42/40 and p-tau immunoassays, to determine abnormal positron emission tomography (PET) signal.

Top Clinical Takeaways

  • The study highlights the effectiveness of a commercially available plasma p-tau217 assay in identifying AD pathology with accuracy comparable to cerebrospinal fluid biomarkers.
  • Implementing a 3-range approach for Aβ positivity based on plasma p-tau217 could substantially reduce confirmatory testing by approximately 80%.
  • Longitudinal analysis shows that plasma p-tau217 values exhibit an annual increase only in individuals with abnormal amyloid (Aβ) pathology.

“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 implementing a 3-range approach for Aβ positivity based on plasma p-tau217,” lead author Nicholas Ashton, PhD, associate professor of neurochemistry at University of Gothenburg in Sweden, and colleagues wrote.1 “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 antiamyloid immunotherapies.”

READ MORE: Limited Diagnostic Utility of Amyloid PET in Distinguishing Cerebral Amyloid Angiopathy from Alzheimer Disease

Investigators assessed data 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).3,4 Participants included patients with and without cognitive impairment grouped by amyloid and tau status using PET or CSF biomarkers. Data were analyzed between February and June of 2023. Researchers assessed patients’MRI, Aβ PET, tau PET, CSF biomarkers, and plasma p-tau217 (ALZpath pTau217 assay). The main outcomes were accuracy of plasma p-tau217 in detection of abnormal amyloid and tau pathology, and longitudinal p-tau217 change according to baseline pathology status.

Using a 3-range reference, investigators observed that the blood test yielded reproducible results and reduced confirmatory testing by approximately 80% in the detection of abnormal Aβ pathology. In addition, researchers reported that plasma p-tau217 values had an annual increase longitudinally only in participants who were Aβ-positive, with the highest increase demonstrated in those with tau positivity.

“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,” Ashton et al noted.1 “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.”

In a similar study presented at the 2023 Alzheimer’s Association International Conference, July 16-20, in Amsterdam, the Netherlands, by Ashton and colleagues, a finger pick blood test showed levels of glial fibrillary acidic protein, neurofilament light, and phosphorylated tau in the veins of participants strongly associated with results from a standard blood analysis. In the study, the blood was collected from 77 memory clinic patients and transferred onto dry blood spot cards that were extracted and measured.5,6

REFERENCES
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
2. Blood Test Appears Promising In Diagnosing Alzheimer’s Disease Before Onset of Symptoms, Could Show Promise In Early Intervention Treatments. News Release. Hackensack Meridian Health. Published January 23, 2024. Accessed February 26, 2024. https://www.newswise.com/articles/blood-test-appears-promising-in-diagnosing-alzheimer-s-disease-before-onset-of-symptoms-could-show-promise-in-early-intervention-treatments
3. Johnson SC, Koscik RL, Jonaitis EM, et al. The Wisconsin Registry for Alzheimer's Prevention: A review of findings and current directions. Alzheimers Dement (Amst). 2017;10:130-142. Published 2017 Dec 8. doi:10.1016/j.dadm.2017.11.007
4. Alcolea D, Clarimón J, Carmona-Iragui M, et al. The Sant Pau Initiative on Neurodegeneration (SPIN) cohort: A data set for biomarker discovery and validation in neurodegenerative disorders. Alzheimers Dement (N Y). 2019;5:597-609. Published 2019 Oct 14. doi:10.1016/j.trci.2019.09.005
5. Huber H, Montoliu-Gaya L, Blennow K, et al. A finger prick collection method for detecting blood biomarkers of neurodegeneration – a pilot study (DROP-AD). Presented at: 2022 Alzheimer’s Association International Conference; July 16 to July 20; Amsterdam, the Netherlands. Abstract 80275.
6. Simple Finger Prick Test Exemplifies Advances in Alzheimer’s Disease Blood Tests. News Release. Alzheimer’s Association. Published July 19, 2023. Accessed February 26, 2024. https://www.prnewswire.com/news-releases/simple-finger-prick-test-exemplifies-advances-in-alzheimers-disease-blood-tests-
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