Biomarkers

Area of Science:

• Neurology
• Biomarker Research
• Neurodegenerative Diseases

Background:

• The latest Alzheimer's disease (AD) criteria integrate tau-PET imaging as a core biomarker.
• The spatial extent of tau pathology is now part of the revised biological staging for AD.
• This study aimed to implement and validate these new criteria in a large cohort.

Purpose of the Study:

• To implement updated Alzheimer's disease (AD) staging criteria incorporating tau-PET in a large research cohort.
• To compare individuals with congruent biological and clinical stages versus those with discrepant stages.
• To investigate the role of co-pathologies and demographics in individuals with mismatched AD stages.

Main Methods:

• 838 amyloid-beta-positive participants from the BioFINDER-2 cohort with tau-PET ([18F]RO948) data were analyzed.
• Participants were classified based on both clinical staging (cognitively normal to dementia) and biological staging (early to advanced).
• Demographics, neurodegeneration markers (cortical thickness, TDP-43 MRI signature, NfL), alpha-synuclein, GFAP, and cerebrovascular lesions were compared between congruent and discrepant staging groups.

Main Results:

• 51.3% of participants showed more advanced clinical impairment than biological stage (Clinical > Biological).
• The Clinical > Biological group was older, had more men, higher alpha-synuclein, elevated NfL, greater TDP-43 atrophy, and more small vessel disease.
• Individuals with more advanced biological stage than clinical (Biological > Clinical) had less neurodegeneration (thicker cortex).

Conclusions:

• The study validates the new AD staging criteria, emphasizing the role of co-pathologies in symptom severity.
• Individuals with less tau pathology than expected for their clinical stage often exhibit significant co-pathologies.
• Measuring non-AD biomarkers is crucial for patients with cognitive impairment disproportionate to their biological AD stage, impacting diagnosis and prognosis.