APOE Genotype Modulates the Relationship Between Plasma p ‐tau217 and Amyloid Burden in Alzheimer's Disease

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BACKGROUND: This study aimed to investigate the differential association between plasma p-tau217 and amyloid burden across Apolipoprotein E (APOE) genotypes. METHODS: F-flortaucipir (FTP) PET, and plasma biomarker assessments, including %p-tau217, p-tau217, and APS2. Participants were categorized based on their APOE genotype: E2+ (E2/E2, E2/E3), E3/E3, and E4+ (E3/E4, E4/E4). The relationship between FBB centiloid values, FTP temporal meta-region-of-interest (ROI) SUVR values, and plasma biomarkers was analyzed across these genotypes, and differences in correlations were assessed using Fisher's Z test. RESULTS: The association between plasma p-tau217 and amyloid burden varied significantly across APOE genotypes. The E2+ group exhibited the strongest correlations between FBB centiloid values and plasma biomarkers (r=0.923 for APS2, r=0.868 for %p-tau217, r=0.826 for p-tau217), which were significantly higher compared to the E4+ group (r=0.741 for APS2, p = 0.010; r=0.661 for %p-tau217, p = 0.037; r=0.538 for p-tau217, p = 0.024). Similarly, the E3/E3 group demonstrated stronger correlations for p-tau217 (r=0.720) compared to the E4+ group (r=0.538; p = 0.028). Additionally, the correlation between FBB centiloid and FTP temporal meta-ROI SUVR was significantly stronger in the E3/E3 group (r=0.698) compared to the E4+ group (r=0.413; p = 0.002). CONCLUSION: This study demonstrates that APOE genotype significantly modulates the relationship between plasma p-tau217 and amyloid burden in Alzheimer's disease. Plasma p-tau217 showed stronger correlations with amyloid burden in individuals with APOE E2 and E3 genotypes compared to those with the E4 genotype, highlighting its potential as a sensitive biomarker for amyloid pathology in non-E4 carriers.

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