Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP)

• Published in: The Journal of nutritional biochemistry 2012-10, Vol.23 (10), p.1214-1223
• Main 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
• Format: Article
• Language: English
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; ADAM10 Protein; Alzheimer disease; Alzheimer Disease - genetics; Alzheimer Disease - pathology; Alzheimer's disease; amyloid; Amyloid beta (Aβ); Amyloid beta-Peptides - metabolism; Amyloid beta-Protein Precursor - genetics; Amyloid beta-Protein Precursor - metabolism; Amyloid precursor protein (APP) processing; Amyloid Precursor Protein Secretases - genetics; Amyloid Precursor Protein Secretases - metabolism; Animals; Aspartic Acid Endopeptidases - genetics; Aspartic Acid Endopeptidases - metabolism; Biological and medical sciences; Cell Line; Cis/trans fatty acids; diet; Feeding. Feeding behavior; Flow Cytometry; Fundamental and applied biological sciences. Psychology; Humans; hydrogenation; Immunoprecipitation; in vitro studies; Lipids; Membrane Glycoproteins - genetics; Membrane Glycoproteins - metabolism; Membrane Proteins - genetics; Membrane Proteins - metabolism; Mice; Neurons - cytology; Nutrition; oils; peptides; Plaque, Amyloid - chemistry; Proteolysis; risk; Ruminantia; ruminants; trans fatty acids; Trans Fatty Acids - adverse effects; Vertebrates: anatomy and physiology, studies on body, several organs or systems
• ISSN: 0955-2863; 1873-4847
• DOI: 10.1016/j.jnutbio.2011.06.015

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.