title: Plasma 24S-hydroxycholesterol levels in elderly subjects with late onset Alzheimer's disease or vascular dementia: a case-control study.
abstract: BACKGROUND
  In central nervous system cholesterol cannot be degraded but is secreted into circulation predominantly in the form of its polar metabolite 24(S)-hydroxycholesterol (24S-OH-Chol). Some studies suggested an association between 24S-OH-Chol metabolism and different neurological diseases including dementia. A possible decrease in 24S-OH-Chol plasma levels has been reported late onset Alzheimer's disease (LOAD) and vascular dementia (VD), but results of previous studies are partially contradictory.
  
  
  METHODS
  By high-speed liquid chromatography/tandem mass spectrometry we evaluated the plasma levels of 24S-OH-Chol in a sample of 160 older individuals: 60 patients with LOAD, 35 patients with VD, 25 subjects affected by cognitive impairment no-dementia (CIND), and 40 (144 for genetics study) cognitively normal Controls. We also investigated the possible association between PPARgamma Pro12Ala polymorphism and dementia or 24S-OH-Chol levels.
  
  
  RESULTS
  Compared with Controls, plasma 24S-OH-Chol levels were higher in LOAD and lower in VD; a slight not-significant increase in CIND was observed (ANOVA p: 0.001). A positive correlation between 24S-OH-Chol/TC ratio and plasma C reactive protein (CRP) levels was found in the whole sample, independent of possible confounders (multiple regression p: 0.04; r2: 0.10). This correlation was strong in LOAD (r: 0.39), still present in CIND (r: 0.20), but was absent in VD patients (r: 0.08). The PPARgamma Pro12Ala polymorphism was not associated with the diagnosis of LOAD, VD, or CIND; no correlation emerged between the Ala allele and 24S-OH-Chol plasma levels.
  
  
  CONCLUSIONS
  Our results suggest that plasma 24S-OH-Chol levels might be increased in the first stages of LOAD, and this phenomenon might be related with systemic inflammation. The finding of lower 24S-OH-Chol concentrations in VD might be related with a more advanced stage of VD compared with LOAD in our sample, and/or to different pathogenetic mechanisms and evolution of these two forms of dementia.
authors.affiliation: Department of Clinical and Experimental Medicine, Section of Internal Medicine, Gerontology and Clinical Nutrition, Azienda Ospedaliero-Universitaria Arcispedale S Anna, Ferrara, Italy. gzuliani@hotmail.com
authors.forename: Giovanni
authors.initials: G
authors.lastname: Zuliani
authors.forename: Michela Perrone
authors.initials: MP
authors.lastname: Donnorso
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosi
authors.forename: Angelina
authors.initials: A
authors.lastname: Passaro
authors.forename: Edoardo
authors.initials: E
authors.lastname: Dalla Nora
authors.forename: Amedeo
authors.initials: A
authors.lastname: Zurlo
authors.forename: Francesco
authors.initials: F
authors.lastname: Bonetti
authors.forename: Alessia F
authors.initials: AF
authors.lastname: Mozzi
authors.forename: Claudio
authors.initials: C
authors.lastname: Cortese
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000097:blood*; D001284:Atrophy / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D060825:Cognitive Dysfunction / Q000097:blood; D015140:Dementia, Vascular / Q000097:blood* / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D008297:Male; D047495:PPAR gamma / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011859:Radiography
chemical_list: D015415:Biomarkers; D006888:Hydroxycholesterols; D047495:PPAR gamma; C044563:24-hydroxycholesterol; D002097:C-Reactive Protein; D002784:Cholesterol