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Alzheimer's & Dementia logoLink to Alzheimer's & Dementia
. 2025 Jan 9;20(Suppl 2):e091452. doi: 10.1002/alz.091452

ABCA7 high‐risk genotype predicts working memory decline among older cognitively healthy African Americans

Mustafa Sheikh 1,, Wiktoria Piaszczynska 1, Alyssa Arnasalam 1, Arcande Oyono 1, José Mojica Perez 1, Miray Budak 1, Bernadette A Fausto 1, Mark A Gluck 1
PMCID: PMC11715817

Abstract

Background

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive cognitive decline1. APOE‐ε4 has been identified as the most prevalent genetic risk factor for the early onset of AD, while ABCA7‐80 (rs115550680) has been shown to have a stronger effect size than the APOE‐ε4 allele and is associated with the development of late‐onset of AD among African Americans2,3. Although the efficiency of executive functions declines with age, some basic attentional functions and preserved knowledge may help mitigate the effects of aging on working memory4. Nevertheless, the impact of APOE ε4 and ABCA7‐80 genotypes on attention and executive function in preclinical AD remains unclear5. This study investigated the influence of APOE ε4 and ABCA7‐80 genotypes on working memory among cognitively unimpaired older African Americans.

Method

Participants were drawn from the ongoing longitudinal study, Pathways to Healthy Aging in African Americans conducted at Rutgers University–Newark. 838 participants (ages ≥ 60) completed saliva collection for genotyping and neuropsychological battery for cognitive assessment with a fraction repeating each assessment multiple times as part of returning visits. Simple linear mixed models were applied for longitudinal statistical analysis.

Result

ABCA7‐80 high‐risk genotype was found to be a risk factor for decreased cognitive performance, as assessed by Trail Making Test Part A (ß = 5.819, p = 0.030) and Part B (ß = 39.964, p < 0.001), Digit Span Total (ß = ‐2.092, p= 0.045), Controlled Oral Word Association (ß = ‐4.708, p = 0.019), as well as a significant association with increased depression.

Conclusion

The ABCA7‐80 high‐risk genotype may indicate early working memory declines in preclinical AD and may serve as a predictive biomarker among cognitively impaired older African Americans.


Articles from Alzheimer's & Dementia are provided here courtesy of Wiley

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