Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP) |
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| Authors: | Grimm Marcus O W Rothhaar Tatjana L Grösgen Sven Burg Verena K Hundsdörfer Benjamin Haupenthal Viola J Friess Petra Kins Stefan Grimm Heike S Hartmann Tobias |
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| Affiliation: | 1. Deutsches Institut für DemenzPrävention (DIDP), Neurodegeneration and Neurobiology, 66421 Homburg, Germany;2. Department of Human Biology and Human Genetics, Technical University of Kaiserslautern, 67663 Kaiserslautern, Germany;3. Experimental Neurology, 66421 Homburg, Germany;1. Departamento de Química-Física-I, Facultad de Ciencias Químicas, UCM, Madrid 28040, Spain;2. R.D. Foundation Group of Institutions, NH-58, Kadrabad, Modinagar, Ghaziabad, India;3. Indian Spectroscopy Society, KC-68/1, Old Kavinagar, Ghaziabad 201 002, India;4. Department of Physics, Arignar Anna Government Arts College, Musiri, Tiruchirappalli 621211, India;1. Clean Combustion Research Group, The School of Aerospace, Mechanical and Mechatronic Engineering, The University of Sydney, NSW 2006, Australia;2. Biofuel Engine Research Facility, Queensland University of Technology, Australia;1. Institute of Pharmaceutical and Medicinal Chemistry, PharmaCampus, Westfälische Wilhelms-University Münster, Corrensstr. 48, 48149 Münster, Germany;2. Heinrich-Heine-University, Department of Rheumatology, Moorenstr. 5, 40225 Düsseldorf, Germany;3. Division of Immunopathology, Department of Pathophysiology and Allergy Research, Medical University of Vienna, Waehringer Guertel 18-20, 1090 Vienna, Austria;1. Department of Electrical Engineering, National Institute of Technology Agartala, India;2. Gandhi Institute for Technological Advancement (GITA), Bhubaneswar, Odisha 752054, India;1. Pediatric Cancer Biology Program, Papé Family Pediatric Research Institute, Department of Pediatrics, Oregon Health & Science University, Portland, OR 97239 USA;1. Departamento de Química-Física I, Facultad de Ciencias Químicas, Universidad Complutense, Madrid 28040, Spain;2. R. D. Foundation Engineering College, NH-58, Kadrabad, Modinagar, Ghaziabad, India |
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| Abstract: | Hydrogenation of oils and diary products of ruminant animals leads to an increasing amount of trans fatty acids in the human diet. Trans fatty acids are incorporated in several lipids and accumulate in the membrane of cells. Here we systematically investigate whether the regulated intramembrane proteolysis of the amyloid precursor protein (APP) is affected by trans fatty acids compared to the cis conformation. Our experiments clearly show that trans fatty acids compared to cis fatty acids increase amyloidogenic and decrease nonamyloidogenic processing of APP, resulting in an increased production of amyloid beta (Aβ) peptides, main components of senile plaques, which are a characteristic neuropathological hallmark for Alzheimer's disease (AD). Moreover, our results show that oligomerization and aggregation of Aβ are increased by trans fatty acids. The mechanisms identified by this in vitro study suggest that the intake of trans fatty acids potentially increases the AD risk or causes an earlier onset of the disease. |
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