When should I order Phosphorylated tau 217 (P-tau 217) in patients with cognitive decline?

When to Order P-tau 217 Testing in Patients with Cognitive Decline

P-tau 217 testing should be ordered in patients with objective cognitive impairment to confirm the presence of Alzheimer's disease pathology, particularly when considering disease-modifying treatments or when the diagnosis is uncertain despite standard clinical evaluation. 1

Clinical Scenarios for P-tau 217 Testing

Recommended Use Cases:

1. Patients with Mild Cognitive Impairment (MCI)

   • P-tau 217 accurately predicts future development of AD dementia in patients with MCI 1
   • High diagnostic accuracy (AUC = 0.80-0.91) for identifying amyloid pathology 2
   • Particularly useful when considering eligibility for disease-modifying treatments 3

2. Differential Diagnosis of Dementia

   • Distinguishing AD from other neurodegenerative disorders
   • Superior performance in discriminating AD from frontotemporal lobar degeneration and vascular dementia (AUC = 0.936,0.892) 4
   • Higher sensitivity (97%) compared to FDG-PET (73%) in early-onset or atypical dementia 5

3. Subjective Cognitive Decline (SCD) with Risk Factors

   • High accuracy (AUC = 0.91) for identifying those with positive CSF Aβ42/40 ratio 2
   • Can detect preclinical AD pathology before clinical symptoms appear 6
   • Useful in patients with family history of AD or APOE ε4 carriers 1

Not Recommended:

• Routine screening in asymptomatic individuals without risk factors
• As a standalone diagnostic test without clinical correlation
• When results would not change management decisions

Interpretation and Follow-up

• Positive P-tau 217: Consider confirmatory testing with CSF biomarkers or amyloid/tau PET when diagnosis remains uncertain 3
• Negative P-tau 217: High negative predictive value (NPV = 0.94-0.98) effectively rules out AD pathology 6
• Borderline Results: Consider additional biomarkers or longitudinal monitoring

Biomarker Combinations

• For optimal diagnostic accuracy, consider combining P-tau 217 with:
  • APOE genotyping in cognitively unimpaired individuals 1
  • Brief cognitive tests for improved prediction of cognitive decline 1
  • Other plasma biomarkers (Aβ42/Aβ40, NfL) depending on clinical context 1

Clinical Pearls and Pitfalls

• Pearl: P-tau 217 outperforms other plasma biomarkers for AD diagnosis, with performance approaching that of CSF and PET biomarkers 1, 4
• Pitfall: Biomarker thresholds vary between assays; use validated assays with established performance characteristics 1
• Pearl: P-tau 217 can predict future cognitive decline, allowing for earlier intervention 6, 7
• Pitfall: Results must be interpreted within clinical context; biomarker positivity alone is insufficient for diagnosis 3

P-tau 217 testing represents a significant advance in the biomarker-based diagnosis of Alzheimer's disease, offering a less invasive alternative to CSF testing and PET imaging with comparable diagnostic accuracy. When used appropriately in the clinical scenarios outlined above, it can improve diagnostic certainty and guide treatment decisions that may impact morbidity, mortality, and quality of life.