| Title: |
Plasma Aβ42/Aβ40 and phospho‐tau217 concentration ratios increase the accuracy of amyloid PET classification in preclinical Alzheimer's disease |
| Authors: |
Rissman, Robert A; Langford, Oliver; Raman, Rema; Donohue, Michael C; Abdel‐Latif, Sara; Meyer, Matthew R; Wente‐Roth, Traci; Kirmess, Kristopher M; Ngolab, Jennifer; Winston, Charisse N; Jimenez‐Maggiora, Gustavo; Rafii, Michael S; Sachdev, Pallavi; West, Tim; Yarasheski, Kevin E; Braunstein, Joel B; Irizarry, Michael; Johnson, Keith A; Aisen, Paul S; Sperling, Reisa A; team, for the AHEAD 3‐45 Study |
| Source: |
urn:ISSN:1552-5260 ; urn:ISSN:1552-5279 ; Alzheimer's & Dementia, 20, 2, 1214-1224 |
| Publisher Information: |
Wiley |
| Publication Year: |
2024 |
| Collection: |
UNSW Sydney (The University of New South Wales): UNSWorks |
| Subject Terms: |
32 Biomedical and Clinical Sciences; 5202 Biological Psychology; 3202 Clinical Sciences; 3209 Neurosciences; 52 Psychology; Acquired Cognitive Impairment; Dementia; Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD); Clinical Research; Biomedical Imaging; Bioengineering; Brain Disorders; Neurosciences; Neurodegenerative; Alzheimer's Disease; Aging; 4.2 Evaluation of markers and technologies; Neurological; Humans; Alzheimer Disease; Amyloid beta-Peptides; Peptide Fragments; Amyloid; tau Proteins; Positron-Emission Tomography; Biomarkers; blood-based biomarkers; mass spectrometry; plasma; tau |
| Description: |
INTRODUCTION: Incorporating blood-based Alzheimer's disease biomarkers such as tau and amyloid beta (Aβ) into screening algorithms may improve screening efficiency. METHODS: Plasma Aβ, phosphorylated tau (p-tau)181, and p-tau217 concentration levels from AHEAD 3-45 study participants were measured using mass spectrometry. Tau concentration ratios for each proteoform were calculated to normalize for inter-individual differences. Receiver operating characteristic (ROC) curve analysis was performed for each biomarker against amyloid positivity, defined by > 20 Centiloids. Mixture of experts analysis assessed the value of including tau concentration ratios into the existing predictive algorithm for amyloid positron emission tomography status. RESULTS: The area under the receiver operating curve (AUC) was 0.87 for Aβ42/Aβ40, 0.74 for phosphorylated variant p-tau181 ratio (p-tau181/np-tau181), and 0.92 for phosphorylated variant p-tau217 ratio (p-tau217/np-tau217). The Plasma Predicted Centiloid (PPC), a predictive model including p-tau217/np-tau217, Aβ42/Aβ40, age, and apolipoprotein E improved AUC to 0.95. DISCUSSION: Including plasma p-tau217/np-tau217 along with Aβ42/Aβ40 in predictive algorithms may streamline screening preclinical individuals into anti-amyloid clinical trials. CLINICALTRIALS: gov Identifier: NCT04468659 HIGHLIGHTS: The addition of plasma phosphorylated variant p-tau217 ratio (p-tau217/np-tau217) significantly improved plasma biomarker algorithms for identifying preclinical amyloid positron emission tomography positivity. Prediction performance at higher NAV Centiloid levels was improved with p-tau217/np-tau217. All models generated for this study are incorporated into the Plasma Predicted Centiloid (PPC) app for public use. |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf |
| Language: |
unknown |
| Relation: |
https://hdl.handle.net/1959.4/unsworks_84925; https://doi.org/10.1002/alz.13542 |
| DOI: |
10.1002/alz.13542 |
| Availability: |
https://hdl.handle.net/1959.4/unsworks_84925; https://unsworks.unsw.edu.au/bitstreams/fd6d0fa6-1fa4-4f84-91a4-21d203285369/download; https://doi.org/10.1002/alz.13542 |
| Rights: |
open access ; https://purl.org/coar/access_right/c_abf2 ; CC BY-NC-ND ; https://creativecommons.org/licenses/by-nc-nd/4.0/ ; free_to_read |
| Accession Number: |
edsbas.34171E08 |
| Database: |
BASE |