Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old

Mengel-From, Jonas; Christensen, Kaare; McGue, Matt; Christiansen, Lene

doi:10.1016/j.neurobiolaging.2010.07.016

« Previous Next »Neurobiology of Aging
Volume 32, Issue 3 , Pages 554.e7-554.e11, March 2011

Genetic variations in the CLU and PICALM genes are associated with cognitive function in the oldest old

Jonas Mengel-From
- The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark
- Department of Clinical Biochemistry and Clinical Genetics, Odense University Hospital, Odense, Denmark
- Corresponding author at: The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, J.B. Winsløws Vej 9, DK-5000 Odense, Denmark. Tel.: +45 6550 4082; fax: +45 6550 3682
Kaare Christensen
- The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark
Matt McGue
- The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark
- Department of Psychology, University of Minnesota, Minneapolis, Minnesota, USA
Lene Christiansen
- The Danish Aging Research Center, Epidemiology Unit, Institute of Public Health, University of Southern Denmark, Odense, Denmark
- Department of Clinical Biochemistry and Clinical Genetics, Odense University Hospital, Odense, Denmark

Received 16 February 2010; received in revised form 7 July 2010; accepted 19 July 2010. published online 26 August 2010.

Abstract

Recently, two large, and independent genome wide association studies of late-onset Alzheimer's disease (AD) established association with the same rs11136000 variation in the clusterin (CLU) gene. In addition, one variation, rs3851179, in the phosphatidylinositol binding clathrin assembly protein (PICALM) gene and one variation, rs6656401, in the complement component (3b/4b) receptor 1 (CR) gene were associated with AD. Here, we replicate these associations with cognitive functioning in 1380 individuals from the Danish (1905) birth cohort study of the oldest old (92–93 years at intake) using measures of Mini Mental State Examination (MMSE) and a cognitive composite score. We found a significant association between the highly frequent CLU rs11136000 T allele (38%) and better performance on the cognitive composite score (p = 0.016) explaining 0.5% of the mean variation in cognitive composite score, and for men a significant association between the highly frequent PICALM rs3851179 A allele (38%). Better performance was found (p = 0.024), explaining 1.4% of the mean variation in cognitive composite score in men. These alleles correspond to the minor alleles initially found more frequent in controls than in cases of AD.

Keywords: Aging, Dementia, Genes