Better Memory and Neural Efficiency in Young Apolipoprotein E ε4 Carriers

Abstract

The apolipoprotein E (APOE) ε4 allele is the major genetic risk factor for Alzheimer's disease, but an APOE effect on memory performance and memory-related neurophysiology in young, healthy subjects is unknown. We found an association of APOE ε4 with better episodic memory compared with APOE ε2 and ε3 in 340 young, healthy persons. Neuroimaging was performed in a subset of 34 memory-matched individuals to study genetic effects on memory-related brain activity independently of differential performance. E4 carriers decreased brain activity over 3 learning runs, whereas ε2 and ε3 carriers increased activity. This smaller neural investment of ε4 carriers into learning reappeared during retrieval: ε4 carriers exhibited reduced retrieval-related activity with equal retrieval performance. APOE isoforms had no differential effects on cognitive measures other than memory, brain volumes, and brain activity related to working memory. We suggest that APOE ε4 is associated with good episodic memory and an economic use of memory-related neural resources in young, healthy human