TY - JOUR
T1 - Effect of apolipoprotein genotype and educational attainment on cognitive function in autosomal dominant Alzheimer’s disease
AU - Langella, Stephanie
AU - Barksdale, N. Gil
AU - Vasquez, Daniel
AU - Aguillon, David
AU - Chen, Yinghua
AU - Su, Yi
AU - Acosta-Baena, Natalia
AU - Acosta-Uribe, Juliana
AU - Baena, Ana Y.
AU - Garcia-Ospina, Gloria
AU - Giraldo-Chica, Margarita
AU - Tirado, Victoria
AU - Muñoz, Claudia
AU - Ríos-Romenets, Silvia
AU - Guzman-Martínez, Claudia
AU - Oliveira, Gabriel
AU - Yang, Hyun Sik
AU - Vila-Castelar, Clara
AU - Pruzin, Jeremy J.
AU - Ghisays, Valentina
AU - Arboleda-Velasquez, Joseph F.
AU - Kosik, Kenneth S.
AU - Reiman, Eric M.
AU - Lopera, Francisco
AU - Quiroz, Yakeel T.
N1 - Publisher Copyright:
© 2023, Springer Nature Limited.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
UR - https://www.scopus.com/pages/publications/85168571169
U2 - 10.1038/s41467-023-40775-z
DO - 10.1038/s41467-023-40775-z
M3 - Article
C2 - 37612284
AN - SCOPUS:85168571169
SN - 2041-1723
VL - 14
JO - Nature communications
JF - Nature communications
IS - 1
M1 - 5120
ER -