Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation.
In: Journal of lipid research, Jg. 52 (2011-05-01), Heft 5, S. 1004-10
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Zugriff:
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.
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Marked accumulation of 27-hydroxycholesterol in the brains of Alzheimer's patients with the Swedish APP 670/671 mutation.
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Autor/in / Beteiligte Person: | Shafaati, M ; Marutle, A ; Pettersson, H ; Lövgren-Sandblom, A ; Olin, M ; Pikuleva, I ; Winblad, B ; Nordberg, A ; Björkhem, I |
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Zeitschrift: | Journal of lipid research, Jg. 52 (2011-05-01), Heft 5, S. 1004-10 |
Veröffentlichung: | 2021- : [New York] : Elsevier ; <i>Original Publication</i>: Memphis, Lipid Research, inc., 2011 |
Medientyp: | academicJournal |
ISSN: | 1539-7262 (electronic) |
DOI: | 10.1194/jlr.M014548 |
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