Biofluid-based staging of Alzheimer's disease.

Area of Science:

• Neurology
• Biomarker Research
• Alzheimer's Disease Diagnostics

Background:

• Conceptual systems for in vivo staging of Alzheimer's disease (AD) using fluid biomarkers are emerging.
• Assessing the clinical and biological relevance of fluid biomarkers for AD staging is crucial.

Purpose of the Study:

• To explore the potential of p-tau217, p-tau205, and NTA-tau for biofluid-based staging of AD pathology.
• To compare biofluid staging with underlying pathology indexed by tau-PET.
• To evaluate concordance between cerebrospinal fluid (CSF) and plasma-based staging.

Main Methods:

• Analysis of p-tau217, p-tau205, and NTA-tau in CSF and plasma samples from the TRIAD cohort.
• Comparison of biofluid staging with tau-PET imaging.
• Assessment of concordance between CSF and plasma staging.

Main Results:

• Good concordance was observed between biofluid staging and underlying AD pathology (minimal, early-to-intermediate, advanced tau tangle deposition).
• Discordant cases were 4.6% (CSF) and 13.3% (plasma).
• CSF and plasma staging matched in 61.7% of cases; 32% showed higher staging in CSF.

Conclusions:

• Biofluid staging of AD using p-tau217, p-tau205, and NTA-tau shows potential for insights into AD hallmarks and disease severity.
• Further research is needed to demonstrate applicability beyond molecular characterization in research settings.