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APOE ε4 lowers age at onset and is a high risk factor for Alzheimer's disease; a case control study from central Norway

Sando, Sigrid Botne; Melquist, Stacey; Cannon, Ashley; Hutton, Michael; Sletvold, Olav; Saltvedt, Ingvild; White, Linda; Lydersen, Stian; Aasly, Jan
Journal article, Peer reviewed
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URI
http://hdl.handle.net/11250/2353209
Date
2008
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  • Institutt for klinisk og molekylær medisin [2067]
  • Institutt for nevromedisin og bevegelsesvitenskap [1709]
  • Publikasjoner fra CRIStin - NTNU [20842]
Original version
BMC Neurology 2008, 8(9)   10.1186/1471-2377-8-9
Abstract
Background: The objective of this study was to analyze factors influencing the risk and timing of

Alzheimer's disease (AD) in central Norway. The APOE ε4 allele is the only consistently identified

risk factor for late onset Alzheimer's disease (LOAD). We have described the allele frequencies of

the apolipoprotein E gene (APOE) in a large population of patients with AD compared to the

frequencies in a cognitively-normal control group, and estimated the effect of the APOE ε4 allele on

the risk and the age at onset of AD in this population.

Methods: 376 patients diagnosed with AD and 561 cognitively-normal control individuals with no

known first degree relatives with dementia were genotyped for the APOE alleles. Allele frequencies

and genotypes in patients and control individuals were compared. Odds Ratio for developing AD

in different genotypes was calculated.

Results: Odds Ratio (OR) for developing AD was significantly increased in carriers of the APOE ε4

allele compared to individuals with the APOE ε3/ε3 genotype. Individuals carrying APOE ε4/ε4 had

OR of 12.9 for developing AD, while carriers of APOE ε2/ε4 and APOE ε3/ε4 had OR of 3.2 and 4.2

respectively. The effect of the APOE ε4 allele was weaker with increasing age. Carrying the APOE

ε2 allele showed no significant protective effect against AD and did not influence age at onset of

the disease. Onset in LOAD patients was significantly reduced in a dose dependent manner from

78.4 years in patients without the APOE ε4 allele, to 75.3 in carriers of one APOE ε4 allele and 72.9

in carriers of two APOE ε4 alleles. Age at onset in early onset AD (EOAD) was not influenced by

APOE ε4 alleles.
Publisher
BioMed Central
Journal
BMC Neurology

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