Temporal Dynamics and Biological Variability of Alzheimer Biomarkers

Area of Science:

• Neurodegenerative Diseases
• Biomarker Discovery
• Diagnostic Imaging

Background:

• Accurate interpretation of Alzheimer disease (AD) findings requires understanding discordance between plasma biomarkers and positron emission tomography (PET).
• Investigating factors influencing these discrepancies is crucial for advancing AD diagnostics and patient management.

Purpose of the Study:

• To compare medical comorbidities, imaging and clinical features, and cognitive changes in individuals with discordant versus concordant plasma biomarker and PET results.
• To elucidate the characteristics of discordance in Alzheimer disease (AD) using both amyloid-beta (Aβ) and tau positron emission tomography (PET) imaging alongside plasma biomarkers.

Main Methods:

• A multicenter cohort study (2016-2023) included 2611 participants with varying cognitive statuses, assessing both plasma biomarkers and Aβ PET imaging.
• Participants were categorized into four groups based on plasma and PET results (plasma-/PET-, plasma+/PET-, plasma-/PET+, plasma+/PET+).
• A subset of 124 participants also underwent tau PET imaging; clinical characteristics and comorbidities were compared across groups, focusing on discordant findings.

Main Results:

• Phosphorylated tau (p-tau) 217 demonstrated high concordance with both Aβ PET (90.5%) and tau PET (83.3%).
• The p-tau217+/Aβ PET- group exhibited older age, higher prevalence of hypertension, diabetes, and chronic kidney disease, along with lower hippocampal volume and a worse clinical trajectory compared to the p-tau217-/Aβ PET- group.
• Discordance in tau PET findings showed fewer significant differences in comorbidities or clinical outcomes, except for faster cognitive deterioration in the p-tau217+/tau PET+ group.

Conclusions:

• The mechanisms underlying plasma biomarker and PET discordance in Alzheimer disease (AD) appear multifaceted.
• Findings highlight the need to consider temporal dynamics and biological variability of plasma biomarkers, particularly p-tau217, in the context of PET imaging.
• These insights are vital for refining diagnostic interpretations and understanding disease progression in AD.