Key result
APOE polymorphisms show no antagonistic pleiotropy for cognition or brain structure across the adult lifespan.
Why the study?
The antagonistic pleiotropy hypothesis proposes that APOE polymorphisms have different effects across the lifespan, conferring benefits earlier in life despite impairments in old age.
Do APOE polymorphisms exhibit antagonistic pleiotropy affecting cognition and brain structure/function across the adult lifespan?
Cohort (n=600)
Do APOE polymorphisms exhibit antagonistic pleiotropy affecting cognition and brain structure/function across the adult lifespan?
APOE polymorphisms do not appear to exhibit antagonistic pleiotropy for cognitive and brain functions across the healthy adult lifespan.
No clinical implications for healthy adults; leaves open APOE effects in disease or pathological aging.
Polymorphisms in the apolipoprotein E (APOE) gene have been associated with individual differences in cognition, brain structure and brain function. For example, the ε4 allele has been associated with cognitive and brain impairment in old age and increased risk of dementia, while the ε2 allele has been claimed to be neuroprotective. According to the 'antagonistic pleiotropy' hypothesis, these polymorphisms have different effects across the lifespan, with ε4, for example, postulated to confer benefits on cognitive and brain functions earlier in life. In this stage 2 of the Registered Report - https://osf.io/bufc4, we report the results from the cognitive and brain measures in the Cambridge Centre for Ageing and Neuroscience cohort (www.cam-can.org). We investigated the antagonistic pleiotropy hypothesis by testing for allele-by-age interactions in approximately 600 people across the adult lifespan (18-88 years), on six outcome variables related to cognition, brain structure and brain function (namely, fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity measured by both functional magnetic resonance imaging and magnetoencephalography). We found no evidence to support the antagonistic pleiotropy hypothesis. Indeed, Bayes factors supported the null hypothesis in all cases, except for the (linear) interaction between age and possession of the ε4 allele on fluid intelligence, for which the evidence for faster decline in older ages was ambiguous. Overall, these pre-registered analyses question the antagonistic pleiotropy of APOE polymorphisms, at least in healthy adults.
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Henson et al. (2020) conducted a cohort in Healthy adults (n=600). APOE polymorphisms vs. Other APOE genotypes was evaluated on Allele-by-age interactions on fluid intelligence, verbal memory, hippocampal grey-matter volume, mean diffusion within white matter and resting-state connectivity. APOE polymorphisms showed no evidence of antagonistic pleiotropy across the adult lifespan for cognition or brain structure, with Bayes factors supporting the null hypothesis.
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