Objective:

To characterize Aβ–tau deposition, evaluate the pathological discriminatory performance of dual-tracer PET for typical amnestic AD, investigate cognitive correlations, and examine the modulatory role of APOE ε4.

Approach:

Key Findings:

• Whole-brain and regional SUVRs for both tracers were significantly higher in AD than in MCI and HC (P<0.001).
• Dual-tracer strategy yielded superior pathological discriminatory efficacy for typical amnestic AD (AUC of 0.97 for AD vs HC, 0.93 for AD vs MCI).
• Tau deposition showed stronger cognitive correlations than Aβ.
• Tau burden and APOE ε4 were independent predictors of cognitive impairment.
• Aβ and tau SUVRs were strongly correlated (r=0.65–0.81), particularly in the precuneus and inferior temporal gyrus.
• APOE ε4 carriers exhibited significantly higher Aβ and tau deposition.

Interpretation:

Sequential ¹⁸F‑AV45/¹⁸F‑AV1451 dual-tracer PET enables accurate in vivo characterization of AD-related Aβ–tau pathology, with standardized combined analysis improving diagnostic capability.

Conclusion:

Dual-tracer PET is a robust tool for clinical AD evaluation, pathological staging, and therapeutic monitoring of typical amnestic AD.

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