apl. Prof. Dr. Dr. rer. nat. Dieter Lütjohann

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1 apl. Prof. Dr. Dr. rer. nat. Dieter Lütjohann Curriculum Vitae A.) Name: General information apl. Prof. Dr. Dr. rer. nat. Dieter Lütjohann Address: Institute of Clinical Chemistry and Pharmacology Laboratory for Special Lipid Analysis/ Center Internal Medicine/UG 68 University Hospital, University of Bonn Sigmund- Freud- Strasse Bonn Phone: +49 (0) Fax: +49 (0) E- mail: bonn.de Date of birth: Nationality: German B.) Scientific career Education/Degrees: 1986 Diploma in Chemistry, University of Bonn 1990 PhD in Chemistry, University of Bonn 2000 PhD in Medical Biochemistry, Karolinska Institute, Stockholm 2002 Assistant Professor in Clinical Biochemistry (Habilitation, Venia legendi) 2003 Degree: Humanpharmakologe (DGPT) 2008 Associate Professor at the Institute of Clinical Chemistry and Clinical Pharmacology, University Clinics Bonn, University of Bonn, Germany Research Experience: Scientific fellow at the Department of Clinical Pharmacology, University of Bonn 1991 Postdoctoral research fellow at the Department of Clinical Chemistry, Karolinska Institute, Huddinge Hospital, Sweden, Paul- Martini- Stiftung scholarship Senior chemist at the Department of Clinical Pharmacology, University of Bonn

2 Postdoctoral research fellow at the Department of Medical Laboratory Sciences and Technology, Division of Clinical Chemistry, Karolinska Institute, Huddinge University Hospital, Huddinge, Sweden, Swedish Medical Research Council scholarship Senior chemist at the Department of Clinical Pharmacology, University of Bonn 2000 Head of the Laboratory of the Department of Clinical Pharmacology, University of Bonn 2008 Head of the Laboratory of Special Lipid Analysis Central Laboratory, Institute of Clinical Chemistry and Pharmacology, University of Bonn Sholarship and Awards: 1989 Young Investigator Poster Award. 44. Tagung der Deutschen Gesellschaft für Verdauungs- und Stoffwechselerkrankungen. Mainz, Germany Paul- Martini- Stiftung scholarship Swedish Medical Research Council scholarship 1996 Poul Astrup Prize 1996 (2 nd price) Nordic Society of Clinical Chemistry together with U. Diczfalusy, E. Lund und I. Björkhem, Torshavn, Faroe Islands, Denmark Investigator Poster Award. Kern Aspen Lipid Conference. Aspen, Co, USA Investigator Poster Award. Kern Aspen Lipid Conference. Aspen, Co, USA. Member of editorial boards: International Journal of Clinical Pharmacology and Therapeutics Biochimica et Biophysica Acta (BBA) Lipid and Lipid Metabolism Referee for scientific journals: Pharmacology, Lipids, Pediatric Research, Journal of Lipid Research, Clinica Chimica Acta, Arteriosclerosis, Thrombosis, and Vascular Biology, Febbs Letters, Clinical Chemistry and Laboratory Medicine, Nature Medicine, Arteriosclerosis, Thrombosis, and Vascular Biology, Lancet Neurology, Public Health and Nutrition, Britisch Journal of Nutrition, Clinical Endocrinology, European Journal of Clinical Pharmacology, International Journal of Neuropsychiatry, Neuroscience Lett, European Journal of Neuroscience, Nutrition and Food Research, Clinical Chemistry and Laboratory Medicine, Future Lipidology, International Journal of Clinical Pharmacology and Therapeutics, Nutrition, Experimental Neurology, Journal of Mass Spectrometry, American Journal of Physiology, Journal of Cellular Biochemistry, Annals of Nutrition and Metabolism, European Heart Journal, Journal of Mass Spectrometry, Pharmacogenetics and Genomics, Biological Chemistry,

3 Memberships: Deutsche Gesellschaft für Atheroskleroseforschung (DGAF) Deutsche Gesellschaft für Experimentelle und Klinische Pharmakologie und Toxikologie e.v. (DGPT) Arbeitsgemeinschaft für Angewandte Humanpharmakologie (AGAH) Austrian Atherosclerosis Society Fundings: EU- Projects : FP6 FP6 FP7 Marie Curie Early Stage Training Programme (MC- EST) - European Graduate School of Neuroscience (EURON) LIPIDIET LIPIDIDIET Industry C.) 30 most important scientific publications 1. Weingärtner, O., Björkhem, I., and Lütjohann, D. (2014) Intestinal Cholesterol Absorption and Cardiovascular Risk, J Am Coll Cardiol, De Nardo, D., Labzin, L. I., Kono, H., Seki, R., Schmidt, S. V., Beyer, M., Xu, D., Zimmer, S., Lahrmann, C., Schildberg, F. A., Vogelhuber, J., Kraut, M., Ulas, T., Kerksiek, A., Krebs, W., Bode, N., Grebe, A., Fitzgerald, M. L., Hernandez, N. J., Williams, B. R., Knolle, P., Kneilling, M., Rocken, M., Lütjohann, D., Wright, S. D., Schultze, J. L., and Latz, E. (2014) High- density lipoprotein mediates anti- inflammatory reprogramming of macrophages via the transcriptional regulator ATF3, Nat Immunol 15, Popp, J., Meichsner, S., Kölsch, H., Lewczuk, P., Maier, W., Kornhuber, J., Jessen, F., and Lütjohann, D. (2013) Cerebral and extracerebral cholesterol metabolism and CSF markers of Alzheimer's disease, Biochem Pharmacol 86, Horenstein, R. B., Mitchell, B. D., Post, W. S., Lütjohann, D., von Bergmann, K., Ryan, K. A., Terrin, M., Shuldiner, A. R., and Steinle, N. I. (2013) The ABCG8 G574R variant, serum plant sterol levels, and cardiovascular disease risk in the Old Order Amish, Arterioscler Thromb Vasc Biol 33, Burg, V. K., Grimm, H. S., Rothhaar, T. L., Grosgen, S., Hundsdorfer, B., Haupenthal, V. J., Zimmer, V. C., Mett, J., Weingärtner, O., Laufs, U., Broersen, L. M., Tanila, H., Vanmierlo, T., Lütjohann, D., Hartmann, T., and Grimm, M. O. (2013) Plant sterols the better cholesterol in Alzheimer's disease? A mechanistical study, J Neurosci 33,

4 6. Bieghs, V., Hendrikx, T., van Gorp, P. J., Verheyen, F., Guichot, Y. D., Walenbergh, S. M., Jeurissen, M. L., Gijbels, M., Rensen, S. S., Bast, A., Plat, J., Kalhan, S. C., Koek, G. H., Leitersdorf, E., Hofker, M. H., Lütjohann, D., and Shiri- Sverdlov, R. (2013) The cholesterol derivative 27- hydroxycholesterol reduces steatohepatitis in mice, Gastroenterology 144, Vanmierlo, T., Weingärtner, O., van der Pol, S., Husche, C., Kerksiek, A., Friedrichs, S., Sijbrands, E., Steinbusch, H., Grimm, M., Hartmann, T., Laufs, U., Bohm, M., de Vries, H. E., Mulder, M., and Lütjohann, D. (2012) Dietary intake of plant sterols stably increases plant sterol levels in the murine brain, J Lipid Res 53, Popp, J., Lewczuk, P., Kölsch, H., Meichsner, S., Maier, W., Kornhuber, J., Jessen, F., and Lütjohann, D. (2012) Cholesterol metabolism is associated with soluble amyloid precursor protein production in Alzheimer's disease, J Neurochem 123, Krawczyk, M., Lütjohann, D., Schirin- Sokhan, R., Villarroel, L., Nervi, F., Pimentel, F., Lammert, F., and Miquel, J. F. (2012) Phytosterol and cholesterol precursor levels indicate increased cholesterol excretion and biosynthesis in gallstone disease, Hepatology 55, Bieghs, V., Wouters, K., van Gorp, P. J., Gijbels, M. J., de Winther, M. P., Binder, C. J., Lütjohann, D., Febbraio, M., Moore, K. J., van Bilsen, M., Hofker, M. H., and Shiri- Sverdlov, R. (2010) Role of scavenger receptor A and CD36 in diet- induced nonalcoholic steatohepatitis in hyperlipidemic mice, Gastroenterology 138, , 2486 e Kenny, E. E., Gusev, A., Riegel, K., Lütjohann, D., Lowe, J. K., Salit, J., Maller, J. B., Stoffel, M., Daly, M. J., Altshuler, D. M., Friedman, J. M., Breslow, J. L., Pe'er, I., and Sehayek, E. (2009) Systematic haplotype analysis resolves a complex plasma plant sterol locus on the Micronesian Island of Kosrae, Proc Natl Acad Sci U S A 106, Wouters, K., van Gorp, P. J., Bieghs, V., Gijbels, M. J., Duimel, H., Lütjohann, D., Kerksiek, A., van Kruchten, R., Maeda, N., Staels, B., van Bilsen, M., Shiri- Sverdlov, R., and Hofker, M. H. (2008) Dietary cholesterol, rather than liver steatosis, leads to hepatic inflammation in hyperlipidemic mouse models of nonalcoholic steatohepatitis, Hepatology 48, Weingärtner, O., Lütjohann, D., Ji, S., Weisshoff, N., List, F., Sudhop, T., von Bergmann, K., Gertz, K., Konig, J., Schafers, H. J., Endres, M., Bohm, M., and Laufs, U. (2008) Vascular effects of diet supplementation with plant sterols, J Am Coll Cardiol 51, Tamboli, I. Y., Prager, K., Thal, D. R., Thelen, K. M., Dewachter, I., Pietrzik, C. U., St George- Hyslop, P., Sisodia, S. S., De Strooper, B., Heneka, M. T., Filippov, M. A., Muller, U., van Leuven, F., Lütjohann, D., and Walter, J. (2008) Loss of gamma- secretase function impairs endocytosis of lipoprotein particles and membrane cholesterol homeostasis, J Neurosci 28, Teunissen, C. E., Floris, S., Sonke, M., Dijkstra, C. D., De Vries, H. E., and Lütjohann, D. (2007) 24S- hydroxycholesterol in relation to disease manifestations of acute experimental autoimmune encephalomyelitis, J Neurosci Res 85,

5 16. Crameri, A., Biondi, E., Kuehnle, K., Lütjohann, D., Thelen, K. M., Perga, S., Dotti, C. G., Nitsch, R. M., Ledesma, M. D., and Mohajeri, M. H. (2006) The role of seladin- 1/DHCR24 in cholesterol biosynthesis, APP processing and Abeta generation in vivo, EMBO J 25, Salen, G., von Bergmann, K., Lütjohann, D., Kwiterovich, P., Kane, J., Patel, S. B., Musliner, T., Stein, P., and Musser, B. (2004) Ezetimibe effectively reduces plasma plant sterols in patients with sitosterolemia, Circulation 109, Wollmer, M. A., Streffer, J. R., Tsolaki, M., Grimaldi, L. M., Lütjohann, D., Thal, D., von Bergmann, K., Nitsch, R. M., Hock, C., and Papassotiropoulos, A. (2003) Genetic association of acyl- coenzyme A: cholesterol acyltransferase with cerebrospinal fluid cholesterol levels, brain amyloid load, and risk for Alzheimer's disease, Mol Psychiatry 8, Vega, G. L., Weiner, M. F., Lipton, A. M., Von Bergmann, K., Lütjohann, D., Moore, C., and Svetlik, D. (2003) Reduction in levels of 24S- hydroxycholesterol by statin treatment in patients with Alzheimer disease, Arch Neurol 60, Papassotiropoulos, A., Streffer, J. R., Tsolaki, M., Schmid, S., Thal, D., Nicosia, F., Iakovidou, V., Maddalena, A., Lütjohann, D., Ghebremedhin, E., Hegi, T., Pasch, T., Traxler, M., Bruhl, A., Benussi, L., Binetti, G., Braak, H., Nitsch, R. M., and Hock, C. (2003) Increased brain beta- amyloid load, phosphorylated tau, and risk of Alzheimer disease associated with an intronic CYP46 polymorphism, Arch Neurol 60, Yu, L., Hammer, R. E., Li- Hawkins, J., Von Bergmann, K., Lütjohann, D., Cohen, J. C., and Hobbs, H. H. (2002) Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion, Proc Natl Acad Sci U S A 99, Sudhop, T.*, Lütjohann, D.*, Kodal, A., Igel, M., Tribble, D. L., Shah, S., Perevozskaya, I., and von Bergmann, K. (2002) Inhibition of intestinal cholesterol absorption by ezetimibe in humans, Circulation 106, Simons, M., Schwarzler, F., Lütjohann, D., von Bergmann, K., Beyreuther, K., Dichgans, J., Wormstall, H., Hartmann, T., and Schulz, J. B. (2002) Treatment with simvastatin in normocholesterolemic patients with Alzheimer's disease: A 26- week randomized, placebo- controlled, double- blind trial, Ann Neurol 52, Sehayek, E., Duncan, E. M., Lütjohann, D., Von Bergmann, K., Ono, J. G., Batta, A. K., Salen, G., and Breslow, J. L. (2002) Loci on chromosomes 14 and 2, distinct from ABCG5/ABCG8, regulate plasma plant sterol levels in a C57BL/6J x CASA/Rk intercross, Proc Natl Acad Sci U S A 99, Locatelli, S., Lütjohann, D.*, Schmidt, H. H., Otto, C., Beisiegel, U., and von Bergmann, K. (2002) Reduction of plasma 24S- hydroxycholesterol (cerebrosterol) levels using high- dosage simvastatin in patients with hypercholesterolemia: evidence that simvastatin affects cholesterol metabolism in the human brain, Arch Neurol 59, Kölsch, H., Lütjohann, D.*, Ludwig, M., Schulte, A., Ptok, U., Jessen, F., von Bergmann, K., Rao, M. L., Maier, W., and Heun, R. (2002) Polymorphism in the

6 cholesterol 24S- hydroxylase gene is associated with Alzheimer's disease, Mol Psychiatry 7, Fassbender, K., Stroick, M., Bertsch, T., Ragoschke, A., Kuehl, S., Walter, S., Walter, J., Brechtel, K., Muehlhauser, F., Von Bergmann, K., and Lütjohann, D. (2002) Effects of statins on human cerebral cholesterol metabolism and secretion of Alzheimer amyloid peptide, Neurology 59, Fassbender, K., Simons, M., Bergmann, C., Stroick, M., Lütjohann, D., Keller, P., Runz, H., Kuhl, S., Bertsch, T., von Bergmann, K., Hennerici, M., Beyreuther, K., and Hartmann, T. (2001) Simvastatin strongly reduces levels of Alzheimer's disease beta - amyloid peptides Abeta 42 and Abeta 40 in vitro and in vivo, Proc Natl Acad Sci U S A 98, Chandalia, M., Garg, A., Lütjohann, D., von Bergmann, K., Grundy, S. M., and Brinkley, L. J. (2000) Beneficial effects of high dietary fiber intake in patients with type 2 diabetes mellitus, N Engl J Med 342, Lütjohann, D., Breuer, O., Ahlborg, G., Nennesmo, I., Siden, A., Diczfalusy, U., and Björkhem, I. (1996) Cholesterol homeostasis in human brain: evidence for an age- dependent flux of 24S- hydroxycholesterol from the brain into the circulation, Proc Natl Acad Sci U S A 93, * contributed equally Stand: 04/2014

Lionel Bretillon,* Dieter Lütjohann,** Lars Ståhle, Torulf Widhe, Lutz Bindl, Gösta Eggertsen,* Ulf Diczfalusy,* and Ingemar Björkhem 1, *

Plasma levels of 24S-hydroxycholesterol reflect the balance between cerebral production and hepatic metabolism and are inversely related to body surface Lionel Bretillon,* Dieter Lütjohann,** Lars Ståhle,