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* Department of Clinical Pharmacology, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
Department of Psychiatry, University of Bonn, Sigmund-Freud-Strasse 25, D-53105 Bonn, Germany
Novartis Pharma AG, CH-4002 Basel, Switzerland
** Center for Molecular Biology, Im Neuenheimer Feld 282, D-69120 Heidelberg, Germany
1 To whom correspondence should be addressed. e-mail: d.luetjohann{at}uni-bonn.de
Cholesterol is implicated to play a role in Alzheimer disease pathology. Therefore, the concentrations of cholesterol, its precursors, and its degradation products in brain homogenates of aging wild-type and ß-amyloid precursor protein transgenic mice carrying the Swedish mutation (APP23) were analyzed. Among the sterols measured, lanosterol is the first common intermediate of two different pathways, which use either desmosterol or lathosterol as the predominant precursors for de novo synthesis of brain cholesterol. In young mice, cholesterol is mainly synthesized via the desmosterol pathway, while in aged mice, lathosterol is the major precursor. 24S-hydroxycholesterol (cerebrosterol), which plays a key role in the removal of cholesterol from the brain, modestly increased during aging.
No differences in the levels of cholesterol, its precursors, or its metabolites were found between wild-type and APP23 transgenic mice. Moreover, the levels of the exogenous plant sterols campesterol and sitosterol were significantly elevated in the brains of APP23 animals at age 12 and 18 months. This time point coincides with abundant plaque formation.
Abbreviations: AD, Alzheimer disease; APP, ß-amyloid precursor protein; BBB, blood-brain-barrier; 
4, epsilon 4; GC-MS, gas chromatography-mass spectrometry; 24S-OH-Chol, 24S-hydroxycholesterol; TMSi, trimethylsilyl
Supplementary key words Alzheimer disease • brain cholesterol metabolism • neurodegeneration • oxysterols • plant sterols
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