APOE Genotype Modifies the Predictive Performance of Plasma Biomarkers for Amyloid Plaque Burden in Subjective...

Apolipoprotein E (APOE) ε4 is a well-known risk factor for Alzheimer's disease (AD), with ε4 carriers exhibiting distinct clinical and biological characteristics compared to non-carriers. This study investigated whether the predictive performance of plasma biomarkers for amyloid positron emission tomography (PET) outcomes varies by APOE ε4 carrier status in individuals with subjective cognitive decline (SCD).

We retrospectively analyzed baseline data from the Cohort Study to Identify Predictors for the Clinical Progression to Mild Cognitive Impairment or Dementia from Subjective Cognitive Decline. Plasma levels of the amyloid beta (Aβ) 42/40 ratio, glial fibrillary acidic protein (GFAP), neurofilament light chain (NfL), and phosphorylated tau (pTau) 181 were quantified using Single Molecule Array technology. We assessed predictive performance of plasma biomarkers for amyloid PET outcomes using receiver operating characteristic analysis and linear regression models.

The study included 104 participants, with 20 APOE ε4 carriers and 84 non-carriers. Among ε4 carriers, NfL (area under the curve [AUC] = 0.909), GFAP (AUC = 0.904), and pTau181 (AUC = 0.828) showed the highest predictive accuracy. For non-carriers, the most predictive biomarkers were pTau181/Aβ42 (AUC = 0.872), Aβ42/Aβ40 (AUC = 0.794), and pTau181 (AUC = 0.761). Significant interactions between APOE and biomarkers were noted for GFAP (P = 0.005) and NfL (P = 0.010) in predicting amyloid plaque burden.

Plasma biomarkers exhibit differential predictive performance for amyloid pathology based on APOE genotype, with GFAP and NfL showing interaction with APOE genotype. These findings suggest the importance of considering APOE genotype when interpreting plasma biomarker results for AD diagnosis in individuals with SCD.

Clinical Research Information Service Identifier: KCT0003397.