Defining patient‐centered amyloid PET thresholds for the onset of tauopathy in Alzheimer's disease

TL;DR

This study identifies personalized amyloid PET thresholds to detect early tauopathy in Alzheimer's disease, considering age and sex differences.

Contribution

The paper introduces patient-centered amyloid PET thresholds for predicting tauopathy onset based on age and sex.

Findings

Younger men show faster amyloid-related tau accumulation.

Amyloid PET thresholds predict earlier tauopathy onset and cognitive decline in women.

Crossing amyloid PET thresholds is linked to progressive tau deposition and cognitive decline.

Abstract

Amyloid‐induced tauopathy drives clinical decline in Alzheimer's disease (AD). Because age and sex shape tau trajectories, defining patient‐centered amyloid thresholds for tauopathy onset could facilitate pre‐tauopathy AD identification and aid treatment decisions and prognosis.

By including two samples (Alzheimer's Disease Neuroimaging Initiative [ADNI, n = 301]; and 18F‐AV‐1451‐A05 [A05, n = 143]), we explored whether age and sex affect tauopathy transition and determined patient‐centered amyloid positron emission tomography (PET) thresholds that mark tauopathy onset.

We found a consistent amyloid PET × age interaction on global tau PET increase in men (ADNI/A05: p = 0.0078/0.018), with younger men showing faster amyloid‐associated tau accumulation. We then established patient‐centered, amyloid PET–inferred tauopathy transition cut‐offs. Women reached this transition at lower amyloid PET levels, and these cutoffs predicted both earlier onset and accelerated cognitive decline (p < 0.001).

This study highlights the effect of age and sex on the amyloid‐to‐tauopathy transition, establishes patient‐centered amyloid PET thresholds for tauopathy onset, and links these thresholds to accelerated cognitive decline.

Younger age is related to faster amyloid‐related tau accumulation in men.We defined a series of amyloid positron emission tomography (PET) thresholds to enable patient‐centered inference of amyloid‐related tauopathy.Crossing the amyloid PET–defined tauopathy phase is associated with more progressive tau deposition and cognitive decline.

Younger age is related to faster amyloid‐related tau accumulation in men.

We defined a series of amyloid positron emission tomography (PET) thresholds to enable patient‐centered inference of amyloid‐related tauopathy.

Crossing the amyloid PET–defined tauopathy phase is associated with more progressive tau deposition and cognitive decline.

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