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: Giovanni Zuliani, Michela Perrone Donnorso, Cristina Bosi, Angelina Passaro, Edoardo Dalla Nora, Amedeo Zurlo, Francesco Bonetti, Alessia F Mozzi, Claudio Cortese
• Journal: BMC neurology (BMC Neurol) Vol. 11 Pg. 121 (Oct 04 2011) ISSN: 1471-2377 [Electronic] England
• PMID: 21970714 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Biomarkers
• Hydroxycholesterols
• PPAR gamma
• 24-hydroxycholesterol
• C-Reactive Protein
• Cholesterol

Topics

• Aged
• Alzheimer Disease (blood)
• Atrophy (pathology)
• Biomarkers (blood)
• Brain (diagnostic imaging, pathology)
• C-Reactive Protein (metabolism)
• Case-Control Studies
• Cholesterol (blood)
• Cognitive Dysfunction (blood)
• Dementia, Vascular (blood, genetics)
• Female
• Genotype
• Humans
• Hydroxycholesterols (blood)
• Male
• PPAR gamma (genetics)
• Polymorphism, Single Nucleotide
• Radiography