On the turnover of brain cholesterol in patients with Alzheimer's disease. Abnormal induction of the cholesterol-catabolic enzyme CYP46 in glial cells.
Evidence is accumulating for a link between cerebral cholesterol metabolism and Alzheimer's disease (AD). Here we focus on a possible relationship between AD and a newly discovered mechanism for cholesterol efflux from the brain, involving conversion of brain cholesterol into 24S-hydroxycholesterol by the neuronal oxidative enzyme CYP46. There was a marked difference in the distribution of CYP46 in brains of control and AD patients. The neuronal cells were less stained in AD brains than in controls while marked positive staining was found in glial cells in AD but not in controls. The dynamic changes in the mechanisms for cholesterol efflux from the brain are of interest in relation to the link between brain cholesterol and amyloid beta-protein in AD.
Bogdanovic
N
N
Division of Geriatric Medicine, Karolinska Institutet, Huddinge University Hospital, Huddinge, Sweden.
Bretillon
L
L
Lund
E G
EG
Diczfalusy
U
U
Lannfelt
L
L
Winblad
B
B
Russell
D W
DW
Björkhem
I
I
D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D001369:Axons / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000378:metabolism*; D000072556:Cholesterol 24-Hydroxylase; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005260:Female; D006801:Humans; D006888:Hydroxycholesterols / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D009457:Neuroglia / Q000201:enzymology* / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D013250:Steroid Hydroxylases / Q000378:metabolism*
D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D000072556:Cholesterol 24-Hydroxylase