Improving the Diagnostic Accuracy of Plasma Alzheimer's Disease Biomarkers With Objective and Subjective Cognitive Screening.
14 affiliations
- 1Vanderbilt Memory & Alzheimer's Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 2Vanderbilt Alzheimer's Disease Research Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 3School of Medicine, Vanderbilt University, Nashville, Tennessee, USA.
- 4Division of Geriatric Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 5Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 6Department of Neurology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
- 7Department of Anatomy and Neurobiology, Boston University Chobanian & Avedisian School of Medicine, Boston, Massachusetts, USA.
- 8Department of Psychiatry and Neurochemistry, Institute of Neuroscience and Physiology, The Sahlgrenska Academy at University of Gothenburg, Gothenburg, Sweden.
- 9Clinical Neurochemistry Lab, Sahlgrenska University Hospital, Mölndal, Sweden.
- 10Department of Molecular Neuroscience, UCL Institute of Neurology, London, UK.
- 11UK Dementia Research Institute at UCL, London, UK.
- 12Department of Pathology and Laboratory Medicine, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA.
- 13Wisconsin Alzheimer's Disease Research Center, University of Wisconsin School of Medicine and Public Health, University of Wisconsin-Madison, Madison, Wisconsin, USA.
- 14Centre for Brain Research, Indian Institute of Science, Bangalore, India.
Abstract
Background
Blood-based biomarkers are increasingly used to identify Alzheimer's disease (AD) pathology and may play an important role in early disease screening and participant selection for clinical trials. However, their performance across stages of cognitive impairment remains unclear. This study examined whether plasma biomarkers differ in their ability to predict amyloid pathology by performance on cognitive screening measures.Methods
Participants were older adults from the community-based Vanderbilt Memory and Aging Project (N = 154; mean age = 72 ± 6 years; 37% MCI). Plasma phosphorylated tau (p-tau)₂₃₁ and glial fibrillary acidic protein (GFAP) were measured using Quanterix Simoa technology. Amyloid positivity was defined by cerebrospinal fluid β-amyloid 42/40 ratio < 0.072. Objective cognitive impairment was defined as ≤ 26 on the Montreal Cognitive Assessment; cognitive complaints were assessed by a single-item self-report. Logistic regression and stratified ROC analyses evaluated associations between biomarkers and amyloid status, with area under the ROC curve (AUC) values compared using DeLong's test.Results
Forty-seven percent of participants were amyloid positive. Higher plasma p-tau₂₃₁ was associated with increased odds of amyloid positivity (OR = 1.18, p < 0.001; AUC = 0.73). Discriminative accuracy was significantly higher among individuals without subjective cognitive concerns (AUC = 0.85) than among those individuals with concerns (AUC = 0.67; p = 0.02). Plasma GFAP was also associated with amyloid positivity (OR = 1.01, p < 0.001; AUC = 0.75) and showed greater accuracy among participants with objective cognitive impairment (AUC = 0.82) compared to unimpaired individuals (AUC = 0.63; p = 0.03).Conclusions
Plasma p-tau₂₃₁ and GFAP were associated with amyloid pathology, but their diagnostic accuracy varied by cognitive screening results, highlighting the value of integrating brief cognitive assessments when interpreting blood-based biomarkers.
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BibTeX
@article{abdolmaleki2026improving,
title = {{Improving the Diagnostic Accuracy of Plasma Alzheimer's Disease Biomarkers With Objective and Subjective Cognitive Screening.}},
author = {Maryam Abdolmaleki and Leslie S Gaynor and Dandan Liu and Timothy J Hohman and Katherine A Gifford and Henrik Zetterberg and Angela L Jefferson and Corey J Bolton},
journal = {Annals of clinical and translational neurology},
year = {2026},
month = oct,
doi = {10.1002/acn3.70565},
url = {https://europepmc.org/article/MED/42957617},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Improving the Diagnostic Accuracy of Plasma Alzheimer's Disease Biomarkers With Objective and Subjective Cognitive Screening.
AU - Maryam Abdolmaleki
AU - Leslie S Gaynor
AU - Dandan Liu
AU - Timothy J Hohman
AU - Katherine A Gifford
AU - Henrik Zetterberg
AU - Angela L Jefferson
AU - Corey J Bolton
PY - 2026
DA - 2026/10/29
JO - Annals of clinical and translational neurology
DO - 10.1002/acn3.70565
UR - https://europepmc.org/article/MED/42957617
AB - Background Blood-based biomarkers are increasingly used to identify Alzheimer's disease (AD) pathology and may play an important role in early disease screening and participant selection for clinical trials. However, their performance across stages of cognitive impairment remains unclear. This study examined whether plasma biomarkers differ in their ability to predict amyloid pathology by performance on cognitive screening measures.Methods Participants were older adults from the community-based Vanderbilt Memory and Aging Project (N = 154; mean age = 72 ± 6 years; 37% MCI). Plasma phosphorylated tau (p-tau)₂₃₁ and glial fibrillary acidic protein (GFAP) were measured using Quanterix Simoa technology. Amyloid positivity was defined by cerebrospinal fluid β-amyloid 42/40 ratio < 0.072. Objective cognitive impairment was defined as ≤ 26 on the Montreal Cognitive Assessment; cognitive complaints were assessed by a single-item self-report. Logistic regression and stratified ROC analyses evaluated associations between biomarkers and amyloid status, with area under the ROC curve (AUC) values compared using DeLong's test.Results Forty-seven percent of participants were amyloid positive. Higher plasma p-tau₂₃₁ was associated with increased odds of amyloid positivity (OR = 1.18, p < 0.001; AUC = 0.73). Discriminative accuracy was significantly higher among individuals without subjective cognitive concerns (AUC = 0.85) than among those individuals with concerns (AUC = 0.67; p = 0.02). Plasma GFAP was also associated with amyloid positivity (OR = 1.01, p < 0.001; AUC = 0.75) and showed greater accuracy among participants with objective cognitive impairment (AUC = 0.82) compared to unimpaired individuals (AUC = 0.63; p = 0.03).Conclusions Plasma p-tau₂₃₁ and GFAP were associated with amyloid pathology, but their diagnostic accuracy varied by cognitive screening results, highlighting the value of integrating brief cognitive assessments when interpreting blood-based biomarkers.
SN - 2328-9503
ER -