Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025
Tau burden is best captured by magnitude and extent: Tau-MaX as a measure of global tau.
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Brown Christopher A, Das Sandhitsu R, Cousins Katheryn A Q, Tropea Thomas F, Plotkin Alice-Chen, Detre John A, Yushkevich Paul A, McMillan Corey T, Lee Edward B, Shaw Leslie M, Nasrallah Ilya M, Alzheimer's Disease Neuroimaging Initiative, Wolk David A
Аннотация
INTRODUCTION: Tau burden consists of both spatial spread and local accumulation, but no study has combined these measures into a single metric to capture overall global tau burden. Here we investigate a new measure combining magnitude and extent-Tau-MaX-as a marker of Alzheimer's disease (AD) severity.
METHODS: A total of 1077 18F-flortaucipir positron emission tomography scans were analyzed using Gaussian mixture models to identify tau+ regions and quantify magnitude of accumulation. We assessed Tau-MaX across the AD spectrum and compared associations of plasma biomarkers and cognition to global Tau-MaX, extent, and magnitude.
RESULTS: Tau-MaX dynamically captured an early shift in spatial spreading to later tau accumulation across the disease spectrum. Tau-MaX had robust associations with plasma biomarkers and cross-sectional and longitudinal cognition. Global Tau-MaX was equivalent to or superior to magnitude or extent measures alone.
DISCUSSION: Tau-MaX provides a region-agnostic measure of global tau burden that can be used to track disease progression across the AD continuum.
HIGHLIGHTS: We measured tau extent, magnitude, and a new combination of these metrics, Tau-MaX. Extent increases early in disease, while magnitude increases in later disease stages. Tau-MaX captures this shift and is closely associated with phosphorylated tau217 and cognition. Global Tau-MaX performed similarly to or better than meta-region of interest tau magnitude or extent. Tau-MaX provides a region-agnostic measure of tau burden to track progression.
METHODS: A total of 1077 18F-flortaucipir positron emission tomography scans were analyzed using Gaussian mixture models to identify tau+ regions and quantify magnitude of accumulation. We assessed Tau-MaX across the AD spectrum and compared associations of plasma biomarkers and cognition to global Tau-MaX, extent, and magnitude.
RESULTS: Tau-MaX dynamically captured an early shift in spatial spreading to later tau accumulation across the disease spectrum. Tau-MaX had robust associations with plasma biomarkers and cross-sectional and longitudinal cognition. Global Tau-MaX was equivalent to or superior to magnitude or extent measures alone.
DISCUSSION: Tau-MaX provides a region-agnostic measure of global tau burden that can be used to track disease progression across the AD continuum.
HIGHLIGHTS: We measured tau extent, magnitude, and a new combination of these metrics, Tau-MaX. Extent increases early in disease, while magnitude increases in later disease stages. Tau-MaX captures this shift and is closely associated with phosphorylated tau217 and cognition. Global Tau-MaX performed similarly to or better than meta-region of interest tau magnitude or extent. Tau-MaX provides a region-agnostic measure of tau burden to track progression.