biostudies-literatureLiu ZNatural Science Foundation of China2859-2867https://www.ebi.ac.uk/biostudies/studies/S-EPMC6866309biostudies-literatureUnknown39(7)Exploring how risk genes cumulatively impair brain function in preclinical phase (i.e., in cognitively normal elderly) could provide critical insights into the pathophysiology of Alzheimer's disease (AD). Working memory impairment has always been a considerable cognitive deficit in AD, which is likely under complex genetic control. Though, the APOE ɛ4 allele could damage the working memory performance in normal elderly, dissociable results have been reported. This allele may exert specific effects in contexts with other genetic variants. The rs2618516 in the spondin 1 gene (SPON1) has been associated with AD risk and brain structure in the elderly. SPON1 may interact with APOE through processing the amyloid precursor protein and suppressing amyloid-β levels. Using neuropsychological tasks Human brain mappingAPOE influences working memory in non-demented elderly through an interaction with SPON1 rs2618516.PMC68663098117346030873458Liu HLi HChen KZhang JPei JMao HYang CDai XLi XLiu ZMa CTao WZhang ZChen YfalseAPOE influences working memory in non-demented elderly through an interaction with SPON1 rs2618516.Exploring how risk genes cumulatively impair brain function in preclinical phase (i.e., in cognitively normal elderly) could provide critical insights into the pathophysiology of Alzheimer's disease (AD). Working memory impairment has always been a considerable cognitive deficit in AD, which is likely under complex genetic control. Though, the APOE ɛ4 allele could damage the working memory performance in normal elderly, dissociable results have been reported. This allele may exert specific effects in contexts with other genetic variants. The rs2618516 in the spondin 1 gene (SPON1) has been associated with AD risk and brain structure in the elderly. SPON1 may interact with APOE through processing the amyloid precursor protein and suppressing amyloid-β levels. Using neuropsychological tasks 2018-01-01T00:00:00Z2018 Jul2026-05-04T02:08:52.459Z2020-06-16T07:14:53ZS-EPMC68663092957304110.1002/hbm.24045