Characterizing amyloid and tau PET-based stages across the clinical continuum

Area of Science:

• Neurology
• Biomarkers
• Medical Imaging

Background:

• Accurate staging of Alzheimer's disease (AD) pathology is crucial for early detection and effective therapeutic trial design.
• Biomarkers like amyloid and tau PET imaging offer objective measures of AD pathology.
• Standardizing PET data across cohorts is essential for reliable staging.

Purpose of the Study:

• To standardize amyloid and tau PET data across multiple cohorts.
• To characterize the frequency of amyloid and tau PET-based stages across the clinical continuum of Alzheimer's disease.
• To investigate the interplay between amyloid, tau, age, and clinical impairment in defining AD progression.

Main Methods:

• Cross-sectional study analyzing data from 10,396 participants with amyloid PET and 3,295 with tau PET.
• Amyloid PET data staged using centiloid bins; tau PET data staged using a hierarchical Braak schema.
• Operationalized PET-based AD biological stages (e.g., Stage A: A+T-; Stage D: A+T56+) and analyzed using ordinal logistic regression.

Main Results:

• Amyloid levels increased with age in cognitively unimpaired and mild cognitive impairment groups.
• In dementia, severe amyloid burden was most common and less associated with age.
• A three-way interaction between amyloid, age, and clinical impairment influenced tau PET severity, with distinct age-related patterns observed.

Conclusions:

• Amyloid and tau PET severity are vital biomarkers for staging and characterizing Alzheimer's disease progression.
• PET-based staging frameworks are feasible for AD diagnosis across diverse tracers and cohorts.
• Age significantly modulates the relationship between amyloid, tau pathology, and clinical presentation in Alzheimer's disease.