Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort

Abstract Introduction Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort. Methods Community-dwelling demen...

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Main Authors: Menayit Tamrat Dresse, Pamela C. L. Ferreira, Akshay Prasadan, Jihui L. Diaz, Xuemei Zeng, Bruna Bellaver, Guilherme Povala, Victor L. Villemagne, M. Ilyas Kamboh, Ann D. Cohen, Tharick A. Pascoal, Mary Ganguli, Beth E. Snitz, C. Elizabeth Shaaban, Thomas K. Karikari
Format: Article
Language:English
Published: BMC 2025-07-01
Series:Alzheimer’s Research & Therapy
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Online Access:https://doi.org/10.1186/s13195-025-01803-w
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author Menayit Tamrat Dresse
Pamela C. L. Ferreira
Akshay Prasadan
Jihui L. Diaz
Xuemei Zeng
Bruna Bellaver
Guilherme Povala
Victor L. Villemagne
M. Ilyas Kamboh
Ann D. Cohen
Tharick A. Pascoal
Mary Ganguli
Beth E. Snitz
C. Elizabeth Shaaban
Thomas K. Karikari
author_facet Menayit Tamrat Dresse
Pamela C. L. Ferreira
Akshay Prasadan
Jihui L. Diaz
Xuemei Zeng
Bruna Bellaver
Guilherme Povala
Victor L. Villemagne
M. Ilyas Kamboh
Ann D. Cohen
Tharick A. Pascoal
Mary Ganguli
Beth E. Snitz
C. Elizabeth Shaaban
Thomas K. Karikari
author_sort Menayit Tamrat Dresse
collection DOAJ
description Abstract Introduction Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort. Methods Community-dwelling dementia-free (n = 113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments. Results Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status, (adjusted odds ratio [AOR] of 1.74*10–24, 1.47, and 3.43*103, respectively (p-values < 0.05), with p-tau217 demonstrating the highest classification accuracy for Aβ-PET status (AUC = 0.94). Plasma p-tau181 and p-tau217 showed significant associations with tau-PET status (AOR: 1.50 and 22.24, respectively (p-values < 0.05), with comparable classification accuracies for tau-PET status (AUC = 0.74 and 0.70, respectively). Only plasma NfL showed significant association with neurodegeneration based on cortical thickness (AOR = 1.09, p-value < 0.05). Conclusion Our findings highlight the potential of plasma p-tau217 as a biomarker for brain Aβ and tau pathophysiology, p-tau181 for tau abnormalities, and NfL for neurodegeneration in the community.
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publishDate 2025-07-01
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series Alzheimer’s Research & Therapy
spelling doaj-art-27f5f5cd40d145f285a7a552f563b4e22025-08-20T03:46:07ZengBMCAlzheimer’s Research & Therapy1758-91932025-07-0117111410.1186/s13195-025-01803-wPlasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohortMenayit Tamrat Dresse0Pamela C. L. Ferreira1Akshay Prasadan2Jihui L. Diaz3Xuemei Zeng4Bruna Bellaver5Guilherme Povala6Victor L. Villemagne7M. Ilyas Kamboh8Ann D. Cohen9Tharick A. Pascoal10Mary Ganguli11Beth E. Snitz12C. Elizabeth Shaaban13Thomas K. Karikari14Department of Epidemiology, School of Public Health, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Statistics & Data Science, Dietrich College of Humanities and Social Sciences, Carnegie Mellon UniversityDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghAlzheimer’s Disease Research Center, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghDepartment of Epidemiology, School of Public Health, University of PittsburghAlzheimer’s Disease Research Center, University of PittsburghDepartment of Epidemiology, School of Public Health, University of PittsburghDepartment of Psychiatry, School of Medicine, University of PittsburghAbstract Introduction Using the ATN framework, we evaluated the potential of plasma biomarkers to identify abnormal brain amyloid-beta (Aβ) positron emission tomography (PET), tau-PET and neurodegeneration in a socioeconomically disadvantaged population-based cohort. Methods Community-dwelling dementia-free (n = 113, including 102 (91%) cognitively normal) participants underwent ATN neuroimaging and plasma biomarker assessments. Results Plasma Aβ42/Aβ40, p-tau181, and p-tau217 showed significant associations with Aβ-PET status, (adjusted odds ratio [AOR] of 1.74*10–24, 1.47, and 3.43*103, respectively (p-values < 0.05), with p-tau217 demonstrating the highest classification accuracy for Aβ-PET status (AUC = 0.94). Plasma p-tau181 and p-tau217 showed significant associations with tau-PET status (AOR: 1.50 and 22.24, respectively (p-values < 0.05), with comparable classification accuracies for tau-PET status (AUC = 0.74 and 0.70, respectively). Only plasma NfL showed significant association with neurodegeneration based on cortical thickness (AOR = 1.09, p-value < 0.05). Conclusion Our findings highlight the potential of plasma p-tau217 as a biomarker for brain Aβ and tau pathophysiology, p-tau181 for tau abnormalities, and NfL for neurodegeneration in the community.https://doi.org/10.1186/s13195-025-01803-wAmyloid betaTau pathologyNeurodegenerationNeuroimagingATN frameworkP-tau217
spellingShingle Menayit Tamrat Dresse
Pamela C. L. Ferreira
Akshay Prasadan
Jihui L. Diaz
Xuemei Zeng
Bruna Bellaver
Guilherme Povala
Victor L. Villemagne
M. Ilyas Kamboh
Ann D. Cohen
Tharick A. Pascoal
Mary Ganguli
Beth E. Snitz
C. Elizabeth Shaaban
Thomas K. Karikari
Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
Alzheimer’s Research & Therapy
Amyloid beta
Tau pathology
Neurodegeneration
Neuroimaging
ATN framework
P-tau217
title Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
title_full Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
title_fullStr Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
title_full_unstemmed Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
title_short Plasma biomarkers identify brain ATN abnormalities in a dementia-free population-based cohort
title_sort plasma biomarkers identify brain atn abnormalities in a dementia free population based cohort
topic Amyloid beta
Tau pathology
Neurodegeneration
Neuroimaging
ATN framework
P-tau217
url https://doi.org/10.1186/s13195-025-01803-w
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