Document Detail


Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation.
MedLine Citation:
PMID:  21335619     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is a significant flux of the neurotoxic oxysterol 27-hydroxycholesterol (27OHC) from the circulation across the blood-brain barrier. Because there is a correlation between 27OHC and cholesterol in the circulation and lipoprotein-bound cholesterol does not pass the blood-brain barrier, we have suggested that 27OHC may mediate the effects of hypercholesterolemia on the brain. We previously demonstrated a modest accumulation of 27OHC in brains of patients with sporadic Alzheimer's disease (AD), consistent with a role of 27OHC as a primary pathogenetic factor. We show here that there is a 4-fold accumulation of 27OHC in different regions of the cortexes of patients carrying the Swedish amyloid precursor protein (APPswe) 670/671 mutation. The brain levels of sitosterol and campesterol were not significantly different in the AD patients compared with the controls, suggesting that the blood-brain barrier was intact in the AD patients. We conclude that accumulation of 27OHC is likely to be secondary to neurodegeneration, possibly a result of reduced activity of CYP7B1, the neuronal enzyme responsible for metabolism of 27OHC. We discuss the possibility of a vicious circle in the brains of the patients with familial AD whereby neurodegenerative changes cause an accumulation of 27OHC that further accelerates neurodegeneration.
Authors:
Marjan Shafaati; Amelia Marutle; Hanna Pettersson; Anita Lövgren-Sandblom; Maria Olin; Irina Pikuleva; Bengt Winblad; Agneta Nordberg; Ingemar Björkhem
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-19
Journal Detail:
Title:  Journal of lipid research     Volume:  52     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-11     Completed Date:  2011-08-03     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1004-10     Citation Subset:  IM    
Affiliation:
Department of Laboratory Medicine Care Sciences and Society, Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Aged
Alzheimer Disease / genetics,  metabolism*
Amyloid beta-Protein Precursor / genetics*
Blotting, Western
Brain / metabolism*
Cholesterol / analogs & derivatives,  metabolism
Female
Humans
Hydroxycholesterols / metabolism*
Male
Middle Aged
Mutation
Phytosterols / metabolism
Sitosterols / metabolism
Grant Support
ID/Acronym/Agency:
AG024336/AG/NIA NIH HHS; GM062882/GM/NIGMS NIH HHS; R01 GM062882/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Amyloid beta-Protein Precursor; 0/Hydroxycholesterols; 0/Phytosterols; 0/Sitosterols; 20380-11-4/27-hydroxycholesterol; 57-88-5/Cholesterol; 5L5O665639/campesterol; 5LI01C78DD/gamma-sitosterol
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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