Biomarkers

Area of Science:

• Neurology and Nephrology
• Biomarker Discovery and Validation

Background:

• Chronic kidney disease (CKD) elevates blood biomarker concentrations, potentially impacting Alzheimer's disease (AD) diagnostics.
• Plasma phosphorylated tau217 (p-tau217) increases with AD pathology, while amyloid beta 1-42 (Aβ42) decreases.
• The influence of reduced estimated glomerular filtration rate (eGFR) on these biomarkers in non-amyloid individuals requires investigation.

Purpose of the Study:

• To assess the association between plasma biomarkers (p-tau217, np-tau217, Aβ42, Aβ40, and their ratios) and decreased eGFR.
• To determine if specific biomarker ratios can mitigate confounding effects of reduced kidney function on AD biomarker measurements.

Main Methods:

• Study included participants with CKD stages 1-4 (eGFR 25-98) confirmed amyloid-PET negative.
• Plasma biomarkers were quantified using immunoprecipitation mass spectrometry.
• Regression analysis modeled the impact of eGFR changes on individual biomarkers and calculated ratios (%p-tau217, Aβ42/Aβ40, p-tau217/Aβ42).

Main Results:

• Decreasing eGFR significantly increased predicted plasma p-tau217 (52%), Aβ42 (16%), and Aβ40 (19%).
• The p-tau217/Aβ42 ratio and %p-tau217 showed smaller predicted increases (31% and 19%, respectively) with decreasing eGFR.
• The Aβ42/Aβ40 ratio did not show a predicted increase, suggesting it is less affected by eGFR changes.

Conclusions:

• The %p-tau217 and, to a lesser extent, the p-tau217/Aβ42 ratio effectively reduce confounding from decreased eGFR compared to p-tau217 alone.
• Aβ42 and Aβ40 also showed reduced predicted increases with decreasing eGFR relative to p-tau217.
• These adjusted ratios offer improved utility for AD biomarker assessment in individuals with impaired kidney function.