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. 2021 Mar 16;96(11):e1491-e1500.
doi: 10.1212/WNL.0000000000011599. Epub 2021 Feb 10.

Amyloid PET Imaging in Self-Identified Non-Hispanic Black Participants of the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Study

Kacie D Deters  1 , Valerio Napolioni  2 , Reisa A Sperling  2 , Michael D Greicius  2 , Richard Mayeux  2 , Timothy Hohman  2 , Elizabeth C Mormino  2
Affiliations

Amyloid PET Imaging in Self-Identified Non-Hispanic Black Participants of the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Study

Kacie D Deters et al. Neurology. .

Abstract

Objective: To examine whether amyloid PET in cognitively normal (CN) individuals screened for the Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) study differed across self-identified non-Hispanic White and Black (NHW and NHB) groups.

Methods: We examined 3,689 NHW and 144 NHB participants who passed initial screening for the A4 study and underwent amyloid PET. The effect of race on amyloid PET was examined using logistic (dichotomous groups) and linear (continuous values) regression controlling for age, sex, and number of APOE ε4 and APOE ε2 alleles. Associations between amyloid and genetically determined ancestry (reflecting African, South Asian, East Asian, American, and European populations) were tested within the NHB group. Potential interactions with APOE were assessed.

Results: NHB participants had lower rates of amyloid positivity and lower continuous amyloid levels compared to NHW participants. This race effect on amyloid was strongest in the APOE ε4 group. Within NHB participants, those with a lower percentage of African ancestry had higher amyloid. A greater proportion of NHB participants did not pass initial screening compared to NHW participants, suggesting potential sources of bias related to race in the A4 PET data.

Conclusion: Reduced amyloid was observed in self-identified NHB participants who passed initial eligibility criteria for the A4 study. This work stresses the importance of investigating AD biomarkers in ancestrally diverse samples as well as the need for careful consideration regarding study eligibility criteria in AD prevention trials.

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Figures

Figure 1
Figure 1. Proportion of Amyloid Positivity and Continuous Amyloid Standardized Uptake Value Ratios (SUVRs) Across APOE Genotypes for the Non-Hispanic Black (NHB) Group
(A) Amyloid positivity. (B) Continuous amyloid SUVRs. The ε2/4 group is shown in this plot but was excluded from statistical analyses. Sample sizes for each NHB genotype are listed, with the subset of individuals classified as amyloid+ in parentheses. Bars are missing for NHB APOE2/2 because there were no NHB individuals with this genotype. Likewise, bars are missing for the non-Hispanic White (NHW) matched APOE2/4 because there were no NHW matched individuals with this genotype. Given that there was just one ε2/2 participant in the NHW matched group, there is no error bar drawn.
Figure 2
Figure 2. Genetic Ancestry Measures for All Anti-Amyloid in Asymptomatic Alzheimer's Disease (A4) Participants and Non-Hispanic Black (NHB) Individuals
(A) All A4 participants. (B) NHB individuals. Data are ranked by African ancestry, with each row representing the ancestry composition of a single individual participant. The non-Hispanic White (NHW) group showed little variance beyond the European ancestry (A), whereas examination of the NHB group revealed a continuum of African ancestry (B).
Figure 3
Figure 3. Plot of Continuous Amyloid PET Standardized Uptake Value Ratios (SUVRs) Compared to Percent African Ancestry, With Amyloid Residualized by Age, Sex, Number of APOE4 Alleles, and Number of APOE2 Alleles
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