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Epistasis between APOE and nicotinic receptor gene CHRNA4 in age related cognitive function and decline

Published online by Cambridge University Press:  24 March 2010

IVAR REINVANG ,
ASTRI J. LUNDERVOLD ,
EIKE WEHLING ,
HELGE ROOTWELT  and
THOMAS ESPESETH
IVAR REINVANG*
Affiliation:
Center for Study of Human Cognition, Department of Psychology, University of Oslo, Norway
ASTRI J. LUNDERVOLD
Affiliation:
Department of Biological and Medical Psychology, University of Bergen, Norway Kavli’s Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway
EIKE WEHLING
Affiliation:
Department of Biological and Medical Psychology, University of Bergen, Norway Kavli’s Research Centre for Aging and Dementia, Haraldsplass Deaconess Hospital, Bergen, Norway
HELGE ROOTWELT
Affiliation:
Department of Medical Biochemistry, Rikshospitalet University Hospital, Oslo, Norway
THOMAS ESPESETH
Affiliation:
Center for Study of Human Cognition, Department of Psychology, University of Oslo, Norway
*
*Correspondence and reprint requests to: Ivar Reinvang, Department of Psychology, Center for the Study of Human Cognition, University of Oslo, Box 1094 Blindern, N-0317 Oslo, Norway. E-mail: [email protected]
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Abstract

Healthy participants (n = 237) aged 45–79 were tested neuropsychologically with tests of memory, speed, and cognitive control and followed up for 3–5 years (mean, 3.4 years). The sample was genotyped for apolipoprotein E (APOE) and CHolinergic Receptor for Nicotine Alpha 4 (CHRNA4), and genetic effects on cognitive function at initial testing and on cognitive decline was studied. We predicted relatively stronger effects of APOE on memory, and of CHRNA4 on speeded tasks. The predictions were partially confirmed, but we found interactive effects of APOE and CHRNA4 in several cognitive domains. Being an APOE ε4/CHRNA4 TT carrier was associated with slower and less efficient performance, and with steeper decline in speed tasks and in delayed recall. Age dependent genetic effects were found for both APOE and CHRNA4, where old participants (60–79 years) showed a negative influence of TT carrier status on initial memory performance, but a tendency for steeper memory decline in ε4 carriers. Inconsistent and small effects of APOE reported in previous studies of healthy groups may be caused by failure to consider epistasis of APOE with nicotinic receptor and other genes. (JINS, 2010, 16, 424–432.)

Keywords

GeneticsAPOEMemorySpeedCognitive controlAgingAcetylcholine
Type
Research Articles
Information
Journal of the International Neuropsychological Society , Volume 16 , Issue 3 , May 2010 , pp. 424 - 432
Copyright
Copyright © The International Neuropsychological Society 2010

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