Cerebrospinal fluid 24S-hydroxycholesterol is increased in patients with Alzheimer's disease compared to healthy controls.
Experiments in cell cultures indicate that accumulation of cholesterol in hippocampal neurons results in an accelerated cleavage of amyloid precursor protein into amyloidogenic components. To be eliminated from the brain, cholesterol is converted to 24S-hydroxycholesterol which may reflect cerebral cholesterol turnover. We investigated cerebrospinal fluid (CSF) concentrations of 24S-hydroxycholesterol in a group of 14 Alzheimer's disease (AD) patients and ten healthy controls without any cognitive deficits or psychiatric or neurological disorders. To exclude potential effects of circulating plasma cholesterol on CSF 24S-hydroxycholesterol levels, only patients and controls with cholesterol levels in the normal range of 150-230 mg/dl were included. We found significantly elevated 24S-hydroxycholesterol CSF but not plasma levels in AD patients compared with healthy controls. Our results demonstrate that CSF 24S-hydroxycholesterol is increased in AD. This effect does not seem to be triggered by plasma cholesterol levels since the latter did not significantly differ between groups.
Schönknecht
Peter
P
Section of Geriatric Psychiatry, Department of Psychiatry, University of Heidelberg, Voss-Strasse 4, 69115, Germany.
Lütjohann
Dieter
D
Pantel
Johannes
J
Bardenheuer
Habertus
H
Hartmann
Tobias
T
von Bergmann
Klaus
K
Beyreuther
Konrad
K
Schröder
Johannes
J
D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid* / Q000235:genetics; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D001057:Apolipoproteins E / Q000235:genetics; D015992:Body Mass Index; D001921:Brain / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D002784:Cholesterol / Q000097:blood*; D005260:Female; D005838:Genotype; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood / Q000134:cerebrospinal fluid*; D006937:Hypercholesterolemia / Q000150:complications / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D000924:Anticholesteremic Agents; D001057:Apolipoproteins E; D006888:Hydroxycholesterols; C044563:24-hydroxycholesterol; D002784:Cholesterol