TY - JOUR
T1 - Dissociable effects of APOE ε4 and β-amyloid pathology on visual working memory
AU - Lu, Kirsty
AU - Nicholas, Jennifer M.
AU - Pertzov, Yoni
AU - Grogan, John
AU - Husain, Masud
AU - Pavisic, Ivanna M.
AU - James, Sarah Naomi
AU - Parker, Thomas D.
AU - Lane, Christopher A.
AU - Keshavan, Ashvini
AU - Keuss, Sarah E.
AU - Buchanan, Sarah M.
AU - Murray-Smith, Heidi
AU - Cash, David M.
AU - Malone, Ian B.
AU - Sudre, Carole H.
AU - Coath, William
AU - Wong, Andrew
AU - Henley, Susie M.D.
AU - Fox, Nick C.
AU - Richards, Marcus
AU - Schott, Jonathan M.
AU - Crutch, Sebastian J.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/11
Y1 - 2021/11
N2 - Although APOE ε4 carriers are at substantially higher risk of developing Alzheimer’s disease than noncarriers1, controversial evidence suggests that APOE ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)2,3. In a population-based cohort born in one week in 1946 (assessed aged 69–71 years), we assessed differential effects of APOE ε4 and β-amyloid pathology (quantified using 18F-Florbetapir-PET) on visual working memory (object–location binding). In 398 cognitively normal participants, APOE ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall, respectively. ε4 carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4 carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer’s disease.
AB - Although APOE ε4 carriers are at substantially higher risk of developing Alzheimer’s disease than noncarriers1, controversial evidence suggests that APOE ε4 might confer some advantages, explaining the survival of this gene (antagonistic pleiotropy)2,3. In a population-based cohort born in one week in 1946 (assessed aged 69–71 years), we assessed differential effects of APOE ε4 and β-amyloid pathology (quantified using 18F-Florbetapir-PET) on visual working memory (object–location binding). In 398 cognitively normal participants, APOE ε4 and β-amyloid had opposing effects on object identification, predicting better and poorer recall, respectively. ε4 carriers also recalled locations more precisely, with a greater advantage at higher β-amyloid burden. These results provide evidence of superior visual working memory in ε4 carriers, showing that some benefits of this genotype are demonstrable in older age, even in the preclinical stages of Alzheimer’s disease.
UR - http://www.scopus.com/inward/record.url?scp=85122359575&partnerID=8YFLogxK
U2 - 10.1038/s43587-021-00117-4
DO - 10.1038/s43587-021-00117-4
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AN - SCOPUS:85122359575
SN - 2662-8465
VL - 1
SP - 1002
EP - 1009
JO - Nature Aging
JF - Nature Aging
IS - 11
ER -