White matter 18F-florbetapir retention predicts cognitive decline and treatment response in Alzheimer’s disease
Publisher DOI
PubMed ID
42218511
Abstract
Purpose
White matter (WM) signal on ¹⁸F-florbetapir positron emission tomography (PET) is often regarded as nonspecific, yet its biological significance remains unclear. This study aimed to characterize the trajectory, clinical significance, and biomarker correlates of normal-appearing white matter (NAWM) ¹⁸F-florbetapir retention across the Alzheimer's disease (AD) continuum.Methods
We analyzed NAWM ¹⁸F-florbetapir retention in 672 participants across the AD continuum from the Alzheimer's Disease Neuroimaging Initiative and two Chinese cohorts. Longitudinal PET, plasma, and cerebrospinal fluid (CSF) biomarkers, as well as lecanemab treatment effects, were evaluated.Results
NAWM retention followed a distinct trajectory from cortical amyloid, increasing during preclinical stages and plateauing in symptomatic phases. Elevated NAWM ¹⁸F-florbetapir retention independently predicted cognitive decline, correlated with plasma p-tau217 and CSF p-tau/Aβ42 ratio, and showed significant reductions following lecanemab therapy. Combined assessment of cortical and NAWM PET improved diagnostic accuracy for amyloid positivity to 92%. NAWM retention also correlated strongly with plasma and CSF biomarkers in preclinical stages, and mediation analyses indicated that these fluid markers partly explained NAWM-cognition associations.Conclusion
NAWM ¹⁸F-florbetapir retention represents a biologically valid and dynamic biomarker of AD progression, with potential utility for early detection, prognostication, and therapeutic monitoring.
White matter (WM) signal on ¹⁸F-florbetapir positron emission tomography (PET) is often regarded as nonspecific, yet its biological significance remains unclear. This study aimed to characterize the trajectory, clinical significance, and biomarker correlates of normal-appearing white matter (NAWM) ¹⁸F-florbetapir retention across the Alzheimer's disease (AD) continuum.Methods
We analyzed NAWM ¹⁸F-florbetapir retention in 672 participants across the AD continuum from the Alzheimer's Disease Neuroimaging Initiative and two Chinese cohorts. Longitudinal PET, plasma, and cerebrospinal fluid (CSF) biomarkers, as well as lecanemab treatment effects, were evaluated.Results
NAWM retention followed a distinct trajectory from cortical amyloid, increasing during preclinical stages and plateauing in symptomatic phases. Elevated NAWM ¹⁸F-florbetapir retention independently predicted cognitive decline, correlated with plasma p-tau217 and CSF p-tau/Aβ42 ratio, and showed significant reductions following lecanemab therapy. Combined assessment of cortical and NAWM PET improved diagnostic accuracy for amyloid positivity to 92%. NAWM retention also correlated strongly with plasma and CSF biomarkers in preclinical stages, and mediation analyses indicated that these fluid markers partly explained NAWM-cognition associations.Conclusion
NAWM ¹⁸F-florbetapir retention represents a biologically valid and dynamic biomarker of AD progression, with potential utility for early detection, prognostication, and therapeutic monitoring.
Date Issued
2026-05-30
Publication Type
Article
Subjects
18F-florbetapir
•
Alzheimer’s disease
•
Biomarkers
•
Cognitive decline
•
Normal-appearing white matter
•
Retention
Language(s)
en
Author(s)
Lin, Huamei | |
Zhang, Ying | |
Wang, Min | |
Jianwei Men | |
Ge, Jingjie | |
Lu, Jiaying | |
Wang, Jing | |
Zhang, Huiwei | |
Yang, Yunhao | |
Zhang, Zhengwei | |
Zhu, Yuhua | |
Zhao, Hongguang | |
Yen, Tzu-Chen | |
Guan, Yihui | |
Fang, Min | |
Yu, Jintai | |
Jiang, Jiehui | |
Zuo, Chuantao |
Additional Credits
Journal
Alzheimer's Research & Therapy
Publisher
BioMed Central
ISSN
1758-9193
Access(Rights)
open.access