Biomarkers

Plasma phosphorylated tau (p-tau) 217 has shown strong performance in detecting β-amyloid (Aβ) positivity on positron emission tomography (PET). However, kidney dysfunction, body mass index (BMI), and anemia are known to affect p-tau217 levels. How the optimal cutoffs for p-tau217 vary in relation to these factors has not been thoroughly explored.

In this multi-center cross-sectional study (2016-2023), 2,571 individuals with unimpaired cognition, mild cognitive impairment, or Alzheimer's-type dementia underwent Aβ PET imaging, plasma p-tau217 measurement (Alzpath Simoa immunoassay), and assessment for estimated glomerular filtration rate (eGFR), BMI, and anemia. Participants were categorized by eGFR (>60, 45-60, and <45 mL/min/1.73 m^2), BMI (underweight, normal weight, obesity, and super-obesity), and anemia (anemia vs. non-anemia). We identified optimal p-tau217 cutoffs for detecting Aβ positivity (PET centiloid ≥25.5) and evaluated accuracy, sensitivity, and specificity in each subgroup.

Optimal p-tau217 cutoffs were elevated in those with kidney dysfunction, underweight or obesity, and anemia compared to the reference groups. Specifically, optimal cutoffs for Aβ positivity were higher among individuals with eGFR <60 (0.635 for eGFR 45-60; 0.935 for eGFR <45) than among those with eGFR >60 (0.425). When the reference cutoff (0.425) was applied in the eGFR <45 group, diagnostic accuracy dropped to 48.3%. Underweight and anemia groups also showed increased optimal cutoffs (0.620 and 0.595) relative to the reference group (0.425), though using the reference cutoff slightly lowered specificity in these groups.

These findings emphasize the importance of tailoring plasma p-tau217 cutoffs based on kidney function, BMI, and anemia status to enhance diagnostic accuracy, especially in populations with more severe kidney dysfunction (eGFR <45).