Objective:

To investigate the potential of phosphorylated tau as a blood-based biomarker for diagnosing systemic amyloidosis.

Key Findings:

• p-tau181 levels were higher in patients with AL or ATTR amyloidosis compared to controls.
• p-tau181 demonstrated moderate diagnostic discrimination with an AUC of 0.82.
• Elevated p-tau181 levels were associated with amyloidosis-related neuropathy.
• p-tau217 also showed elevation in amyloidosis patients, distinguishing them from controls.
• p-tau181 levels increased in asymptomatic individuals with pathogenic ATTR variants as they approached predicted disease onset.

Interpretation:

Circulating phosphorylated tau may serve as a valuable diagnostic tool for systemic amyloidosis, particularly in differentiating amyloid-related neuropathy from other conditions.

Limitations:

• Further studies are needed to validate the findings and integrate biomarkers into diagnostic workflows.
• The study was conducted in specific cohorts, which may limit generalizability.

Conclusion:

Phosphorylated tau has potential diagnostic value in systemic amyloidosis and warrants further investigation.