Biological Psychology/Pharmacopsychology Editor: P. Netter (Giessen) Original Paper Neuropsychobiology 2003;48:35–40 DOI: 10.1159/000071827 The Combined Effects of Apolipoprotein E Polymorphism and Low-Density Lipoprotein Cholesterol on Cognitive Performance in Young Adults Sampsa Puttonen a Marko Elovainio a Mika Kivimäki a Terho Lehtimäki b Liisa Keltikangas-Järvinen a a Department of Psychology, University of Helsinki, Helsinki, b Laboratory of Atherosclerosis Genetics, Department of Clinical Chemistry, Centre for Laboratory Medicine, University Hospital of Tampere, and Tampere University Medical School, Department of Clinical Chemistry, Tampere, Finland Liisa Keltikangas-Järvinen Department of Psychology, University of Helsinki, PO Box 13 FI–00014 Helsinki (Finland) Tel. +358 9 19123246, Fax +358 9 19123379 E-Mail Liisa.Keltikangas-Jarvinen@helsinki.fi ABC Fax + 41 61 306 12 34 E-Mail karger@karger.ch www.karger.com © 2003 S. Karger AG, Basel 0302–282X/03/0481–0035$19.50/0 Accessible online at: www.karger.com/nps Key Words Apolipoprotein E W Cognitive performance W Low-density lipoprotein Abstract This study examined the relations of apolipoprotein E (ApoE) genotype and the low-density lipoprotein (LDL) cholesterol level to cognitive performance of 57 random- ly selected healthy young adults. From the ongoing pop- ulation-based study of Cardiovascular Risk in Young Finns, 25 men and 32 women were ApoE genotyped and participated in mental arithmetic and reaction time tasks. In contrast to findings obtained from studies with elderly subjects, ApoE4 polymorphism was associated with bet- ter cognitive performance. In addition, LDL cholesterol moderated this association. In the ApoE4 genotype group, low LDL cholesterol was associated with good performance in the mental arithmetic test, whereas for those without ApoE4 genotype, low LDL cholesterol was associated with poor performance. Performance in the reaction time task did not differ between the ApoE groups. In conclusion, assessment of the influence of ApoE on cognitive performance may require taking addi- tional physiological factors, such as the level of choles- terol, into account. Copyright © 2003 S. Karger AG, Basel Introduction Apolipoprotein E (ApoE) is a polymorphic protein arising from 3 alleles (Â2, Â3 and Â4) at a single gene locus. This polymorphic glycoprotein plays a critical role in tri- glyceride-rich lipoprotein catabolism and cholesterol ho- meostasis [1]. Its 3 major isoforms, ApoE4, ApoE3, and ApoE2, differ from one another only by single amino acid substitutions, yet these changes have profound functional consequences both at the cellular and molecular levels. ApoE3 seems to be the normal isoform in all known func- tions, whereas either ApoE4 or ApoE2 can be dysfunc- tional [2]. ApoE has emerged as an important molecule in several biological processes that are not directly related to its lipid transport function. These processes may relate e.g. to Alz- heimer’s disease, immunoregulation, cardiovascular res-