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

TL;DR

This study shows that the APOE gene type affects how well plasma p-tau217 reflects amyloid buildup in Alzheimer's disease.

Contribution

The study reveals that plasma p-tau217's correlation with amyloid burden varies significantly by APOE genotype, particularly in non-E4 carriers.

Findings

The E2+ group showed the strongest correlations between plasma p-tau217 and amyloid burden.

E3/E3 carriers had stronger p-tau217 correlations than E4+ carriers.

Plasma p-tau217 is a more sensitive biomarker for amyloid pathology in non-E4 carriers.

Abstract

This study aimed to investigate the differential association between plasma p‐tau217 and amyloid burden across Apolipoprotein E (APOE) genotypes.

A total of 234 participants were included in the study, undergoing 18F‐florbetaben (FBB), 18F‐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.

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).

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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