title: APOE genotype and cholesterol levels in lewy body dementia and Alzheimer disease: investigating genotype-phenotype effect on disease risk.
abstract: BACKGROUND
  APOE is the most recognized genetic risk factor for sporadic late-onset Alzheimer disease (AD). The role of APOE genotype in Lewy body dementia (LBD) is still unknown as well as the relationship between APOE genotype and cholesterol levels.
  
  
  OBJECTIVE
  The objective of this study was to explore the association between APOE genotype and cholesterol levels in patients with LBD and those with AD.
  
  
  METHODS
  Eighty-two patients with LBD were consecutively enrolled as well as a comparable number of patients with AD and comparison group. Each subject underwent a clinical and neuropsychologic evaluation and APOE genotyping.
  
  
  RESULTS
  The distribution of APOE genotypes significantly differed between AD and LBD cases compared with the comparison group, with the APOE epsilon4+ (epsilon4+/epsilon4 + or epsilon4+/epsilon4-) genotype more frequent in patient subgroups. Different models have been fitted, and total APOE epsilon4-hypercholesterolemia complete interaction effect was claimed in predicting their relationship on disease outcome. Subjects with hypercholesterolemia and heterozygous for APOE epsilon4 allele had more than threefold risk to develop AD compared both with the comparison group and with those with LBD. The risk to develop AD in hypercholesterolemic and APOE epsilon4 homozygous subjects was 13-fold compared with the comparison group and those with LBD. Conversely, there was not evidence for APOE epsilon4-hypercholesterolemia complete interaction effect in LBD and in the comparison group.
  
  
  CONCLUSIONS
  This study highlighted that APOE is a risk factor not only for AD, but also for LBD, and that the APOE-cholesterol pathway differently affects AD and LBD. This approach may aid the search for the identification of an interactive effect of APOE genotype and modifiable risk factors, i.e., hypercholesterolemia, eventually resulting in individualized and effective cholesterol-lowering therapy in at-risk subjects.
authors.affiliation: Centre for Ageing Brain and Dementia, Department of Neurology, the III Laboratory of Biotechnology and Department of Biochemistry, University of Brescia, Brescia, Italy. bborroni@inwind.it
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Mario
authors.initials: M
authors.lastname: Grassi
authors.forename: Chiara
authors.initials: C
authors.lastname: Costanzi
authors.forename: Silvana
authors.initials: S
authors.lastname: Archetti
authors.forename: Luigi
authors.initials: L
authors.lastname: Caimi
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
mesh_terms: D000544:Alzheimer Disease / Q000453:epidemiology / Q000235:genetics*; D053327:Apolipoprotein E4 / Q000235:genetics*; D001057:Apolipoproteins E / Q000235:genetics*; D002784:Cholesterol; D014644:Genetic Variation; D005838:Genotype; D020961:Lewy Body Disease / Q000453:epidemiology / Q000235:genetics*; D008957:Models, Genetic; D010641:Phenotype; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E; D002784:Cholesterol