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Article Abstract
Introduction: Apolipoprotein E (APOE) and ABCA7 genes are among the strongest heritable risk factors for Alzheimer's disease (AD) in African-ancestry (AA) populations. APOE 𝜀4 affects both risk and age at onset (AAO), with lower risk in AA populations. This study evaluates the independent and interactive effects of the AA-specific ABCA7 frameshift deletion and APOE 𝜀4 allele on AAO.
Methods: We analyzed 3510 AA individuals, including AD cases and controls. Cox regression models assessed the effects of ABCA7 deletion, APOE genotypes, and their interactive influence on AAO.
Results: APOE ε3/ε4 carriers with the ABCA7 deletion had a significantly shorter survival compared to ε3/ε4 carriers without the deletion. No significant differences were found between deletion carriers and non-carriers with APOE ε3/ε3 or ε4/ε4 genotypes.
Discussion: Our study showed that the ABCA7 deletion lowered the AAO of AD in APOE ε3/ε4 carriers from AA populations. These findings suggest that the AA-specific ABCA7 deletion and the APOE ε4 allele have synergistic effects on AAO.
Highlights: AA-specific ABCA7 deletion lowers AAO of AD in APOE ε3/ε4 carriers from AA populations. Findings suggest an interaction between ABCA7 deletion and APOE ε4 on AAO. APOE ε4 has a strong, dose-dependent effect on AAO of AD in AA individuals. ABCA7 deletion impact on AAO of AD is stronger in females with APOE ε3/ε4.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC12365657 | PMC |
| http://dx.doi.org/10.1002/alz.70583 | DOI Listing |
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