What are the next steps after a positive phospho-tau 217 (ptau-217) result?

Next Steps After a Positive P-tau217 Result

After a positive p-tau217 result, the next step should be confirmatory testing with additional biomarkers such as CSF biomarkers (Aβ42/Aβ40 ratio, p-tau) or amyloid/tau PET imaging, particularly when considering disease-modifying treatments or in cases of diagnostic uncertainty. 1

Understanding the Significance of Positive P-tau217

P-tau217 is a highly accurate plasma biomarker for detecting Alzheimer's disease pathology, with:

• 82% sensitivity and 86% specificity for detecting amyloid pathology
• 83% sensitivity and 83% specificity for detecting tau pathology 1, 2

This biomarker shows dose-response relationships with brain-wide tau accumulation and increases gradually during both preclinical and prodromal stages of Alzheimer's disease 1.

Recommended Clinical Algorithm Following Positive P-tau217

1. Confirm AD pathology with additional biomarkers:

   • CSF biomarkers (Aβ42/Aβ40 ratio, p-tau)
   • Amyloid PET imaging
   • Tau PET imaging 1

2. Comprehensive cognitive assessment:

   • Combining p-tau217 with brief cognitive tests significantly improves diagnostic accuracy 1
   • P-tau217 levels correlate negatively with memory performance in symptomatic AD 3

3. Consider APOE genotyping:

   • Combining p-tau217 with APOE genotyping improves diagnostic accuracy 1

4. Evaluate for disease-modifying treatment eligibility:

   • Anti-amyloid antibody therapies like donanemab and aducanumab have demonstrated reduction in p-tau217 levels 1

5. Establish baseline for longitudinal monitoring:

   • P-tau217 can be used to track disease progression and treatment response over time 1

Important Clinical Considerations

Strengths of P-tau217

• Plasma p-tau217 has diagnostic performance comparable to CSF p-tau217 for detecting amyloid pathology (AUC = 91% vs. 94%) 4
• It outperforms other plasma biomarkers (p-tau181, p-tau231) for AD diagnosis 1
• Shows exceptional diagnostic accuracy even at early stages of AD 3

Limitations and Caveats

• Not all individuals with elevated p-tau217 will progress to symptomatic Alzheimer's disease 1
• Current sensitivity and specificity are inadequate for broad clinical use in asymptomatic individuals 1
• Approximately 15-30% of cognitively unimpaired individuals over 60 years of age exhibit cerebral Aβ pathology changes detectable by p-tau217 1
• Diagnostic accuracy is higher in cognitively impaired individuals compared to cognitively unimpaired individuals 2

Assay Selection

• Use only high-performing, validated p-tau217 assays, as performance varies significantly between different assays 1
• Most available p-tau217 immunoassays have similar performance 5

Patient Communication

When discussing p-tau217 results with patients:

• Explain that a positive result confirms AD pathology
• A negative result has a high negative predictive value (NPV = 0.94-0.98) to rule out AD pathology
• Borderline results should be interpreted with caution and may require additional biomarkers or longitudinal monitoring 1
• Discuss the ethical implications of biomarker results, given the uncertainty of individual prediction 1

Remember that biomarker results alone are insufficient for management decisions, and should be integrated with clinical assessment and other diagnostic information 1.