Tau burden is best captured by magnitude and extent: Tau-MaX as a measure of global tau

Abstract

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.