Biomarkers

Area of Science:

• Neuroscience
• Biomarkers of Alzheimer's Disease
• Neuroimaging Analysis

Background:

• Tau burden is variable after amyloid positivity (A+) onset and correlates with clinical decline in sporadic Alzheimer's Disease (AD).
• Understanding factors influencing amyloid-related tau accumulation is crucial for AD progression insights.

Purpose of the Study:

• To investigate common factors that accelerate amyloid-related tau accumulation using temporal modeling and neuroimaging data.
• To analyze the influence of age, APOE-e4 carriage, sex, and education on tau accumulation trajectories.

Main Methods:

• Utilized PET imaging data from three cohorts (ADNI, OASIS, WISC) with amyloid (A+) and tau (T+) quantification.
• Estimated age at amyloid positivity onset (EAOA) and time since A+ onset (A+ time).
• Employed linear mixed-effects models (LMEs) to assess associations between A+ time and tau SUVR, including interactions with demographic and genetic factors.

Main Results:

• A+ time positively associated with tau SUVR in medial temporal and temporal neocortex across cohorts.
• APOE-e4 carriage significantly interacted with A+ time, accelerating medial temporal tau accumulation.
• Sex and baseline tau age also showed significant interactions with A+ time, influencing tau trajectories, particularly in females and younger individuals.

Conclusions:

• APOE-e4 carriage consistently accelerates tau trajectories relative to A+ onset in longitudinal AD cohorts.
• Findings underscore the role of genetic factors (APOE-e4) in modulating AD-related tau pathology.
• Further research is needed to explore cohort-specific differences and refine understanding of these relationships.