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

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 ¹⁸ F‐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.