Developing Topics.

Background: Addition of apolipoprotein E4 (ApoE4) proteotype (as a surrogate for high-risk APOE ɛ4 genotype) has significantly improved models that use the plasma Aβ42/40 ratio to predict Aβ PET-positivity, but studies suggest different ethnicities may be less affected by the addition. Our objective was to assess the influence ApoE4 proteotype in a predominantly Hispanic cohort of participants.

Method: Participants in this study (n = 250) underwent neurological and neuropsychological evaluations and amyloid PET brain scans (SUVR data and visual reads) at the 1Florida ADRC; they also underwent blood draws for ApoE4 proteotyping and Aβ42/40 ratio determination by LC-MS/MS performed at Quest Diagnostics. Ethnicity was self-reported as Hispanic or non-Hispanic. Using logistic regression analysis and Delong's test, we examined the effect of incorporating ApoE4 proteotype as a categorical variable on AUCs for the overall population and for participants stratified by ethnicity: Hispanic vs non-Hispanic. Statistical analyses were conducted using R statistical software version 4.3.3. Two-tailed P-values <0.05 were considered statistically significant.

Result: The ADRC cohort had roughly 3-times the percentage of Hispanic participants (about 60% of both the Aβ PET-positive and Aβ PET-negative participants) compared with a previous Aβ42/40 LC-MS/MS study that incorporated ApoE4 proteotype. Based on ApoE4 proteotype, incorporating APOE4 allele count modestly but significantly increased the AUC (95% CI) from 0.84 (0.79-0.89) to 0.86 (0.82-0.91), P = 0.038, Figure A. Subsetting the ADRC cohort participants into Hispanic vs non-Hispanic ethnicity provided a contrasting effect for ApoE4 proteotype on model improvement. For Hispanic participants, the AUC (95% CI) for the ratio plus ApoE4 proteotype, 0.86 (0.80 to 0.92) and the Aβ42/40 ratio alone, 0.85 (0.78-0.91) were not significantly different (P = 0.306), Figure B. For non-Hispanic participants, the AUC (95% CI) for the ratio plus ApoE4 proteotype, 0.87 (0.81-0.94) was significantly higher (P = .048) than the Aβ42/40 ratio alone, 0.83 (0.75- 0.91), Figure C.

Conclusion: ApoE4 proteotype did not improve prediction of PET positivity by plasma Aβ42/40 in the Hispanic subcohort, suggesting that adding APOE4 to Aβ42/40 in algorithms used in Alzheimer's disease risk assessment may not improve PET-prediction for all races and ethnicities.