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Genetic variation in apolipoprotein D and Alzheimer’s disease

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Abstract.

Apolipoprotein D (apoD) is a lipoprotein–associated glycoprotein, structurally unrelated to apoE, that transports small hydrophobic ligands including cholesterol and sterols. Levels are increased in the hippocampus and CSF of Alzheimer’s disease (AD) patients. We tested whether variation in the APOD gene affects AD risk. Four single nucleotide polymorphisms (SNPs) were investigated (in map order): exon 2, 15T→C encodes an amino acid substitution Phe→Ser at codon 15; intron 2, –352G→A; intron 3, +45C→T; intron 4, +718C→T, determined by SNaPshot assay. SNP frequencies for 394 eastern Finnish AD patients were compared with those found for 470 control subjects, dividing subjects also into early–onset AD (EOAD; ≤ 65 years) and late–onset AD (LOAD; >65 years) groups. The –352G allele was associated with a significant 3–fold increase in the risk of EOAD (OR: 2.7; 95% CI: 1.1–6.5). The –352G containing haplotypes were more common for EOAD cases (TGCC: 0.48 vs 0.41; TGCT: 0.08 vs 0.01 (p = 0.002). In the Grade–of–membership analysis, APOD genotype frequencies at each SNP site and disease status were used to construct two latent groups: the affected group carried –352 as GG or GA and +45 CC, was often women and enriched in APOE ε4. Each method suggested that the –352G allele frequency is higher for EOAD in the eastern Finnish population.

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Authors and Affiliations

  1. Dept. of Neuroscience & Neurology, University Hospital and University of Kuopio, Kuopio, Finland

    S. Helisalmi PhD, M. Hiltunen, S. Vepsäläinen, S. Iivonen, M. Lehtovirta, A. M. Koivisto & H. Soininen

  2. Brain Research Unit, Clinical Research Centre/Mediteknia University of Kuopio, Kuopio, Finland

    S. Helisalmi PhD, M. Hiltunen, S. Vepsäläinen, S. Iivonen, A. M. Koivisto & H. Soininen

  3. Dept. of Neuroscience & Neurology, Brain Research Unit Clinical Research Centre/Mediteknia Kuopio University , Tel.: E-Mail: , Harjulantie 1, 70211, Kuopio, Finland

    S. Helisalmi PhD

  4. Center for Demographic Studies, Duke University, Durham (NC), USA

    E. H. Corder

  5. Dept. of Neurology, Jorvi Hospital, Espoo, Finland

    M. Lehtovirta

  6. Dept. of Pathology & Forensic, Medicine University Hospital & University of Kuopio, Kuopio, Finland

    A. Mannermaa

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  1. S. Helisalmi PhD
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  2. M. Hiltunen
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  7. A. Mannermaa
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  8. A. M. Koivisto
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  9. H. Soininen
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Correspondence to S. Helisalmi PhD.

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Helisalmi, S., Hiltunen, M., Vepsäläinen, S. et al. Genetic variation in apolipoprotein D and Alzheimer’s disease. J Neurol 251, 951– 957 (2004). https://doi.org/10.1007/s00415-004-0470-8

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  • DOI: https://doi.org/10.1007/s00415-004-0470-8

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