Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease

Stephanie Langella, N. Gil Barksdale, Daniel Vasquez, David Aguillon, Yinghua Chen, Yi Su, Natalia Acosta-Baena, Juliana Acosta-Uribe, Ana Y. Baena, Gloria Garcia-Ospina, Margarita Giraldo-Chica, Victoria Tirado, Claudia Muñoz, Silvia Ríos-Romenets, Claudia Guzman-Martínez, Gabriel Oliveira, Hyun-Sik Yang, Clara Vila-Castelar, Jeremy J. Pruzin, Valentina Ghisays, Joseph F. Arboleda-Velasquez, Kenneth S. Kosik, Eric M. Reiman, Francisco Lopera and Yakeel T. Quiroz ()
Additional contact information
Stephanie Langella: Harvard Medical School
N. Gil Barksdale: Harvard Medical School
Daniel Vasquez: Universidad de Antioquia
David Aguillon: Universidad de Antioquia
Yinghua Chen: Banner Alzheimer’s Institute
Yi Su: Banner Alzheimer’s Institute
Natalia Acosta-Baena: Universidad de Antioquia
Juliana Acosta-Uribe: Universidad de Antioquia
Ana Y. Baena: Universidad de Antioquia
Gloria Garcia-Ospina: Universidad de Antioquia
Margarita Giraldo-Chica: Universidad de Antioquia
Victoria Tirado: Universidad de Antioquia
Claudia Muñoz: Universidad de Antioquia
Silvia Ríos-Romenets: Universidad de Antioquia
Claudia Guzman-Martínez: Universidad de Antioquia
Gabriel Oliveira: Harvard Medical School
Hyun-Sik Yang: Harvard Medical School
Clara Vila-Castelar: Harvard Medical School
Jeremy J. Pruzin: Banner Alzheimer’s Institute
Valentina Ghisays: Banner Alzheimer’s Institute
Joseph F. Arboleda-Velasquez: Harvard Medical School
Kenneth S. Kosik: University of California Santa Barbara
Eric M. Reiman: Banner Alzheimer’s Institute
Francisco Lopera: Universidad de Antioquia
Yakeel T. Quiroz: Harvard Medical School

Nature Communications, 2023, vol. 14, issue 1, 1-8

Abstract: Abstract Autosomal dominant Alzheimer’s disease (ADAD) is genetically determined, but variability in age of symptom onset suggests additional factors may influence cognitive trajectories. Although apolipoprotein E (APOE) genotype and educational attainment both influence dementia onset in sporadic AD, evidence for these effects in ADAD is limited. To investigate the effects of APOE and educational attainment on age-related cognitive trajectories in ADAD, we analyzed data from 675 Presenilin-1 E280A mutation carriers and 594 non-carriers. Here we show that age-related cognitive decline is accelerated in ADAD mutation carriers who also have an APOE e4 allele compared to those who do not and delayed in mutation carriers who also have an APOE e2 allele compared to those who do not. Educational attainment is protective and moderates the effect of APOE on cognition. Despite ADAD mutation carriers being genetically determined to develop dementia, age-related cognitive decline may be influenced by other genetic and environmental factors.

Date: 2023
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DOI: 10.1038/s41467-023-40775-z

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