Trans fatty acids enhance amyloidogenic processing of the Alzheimer amyloid precursor protein (APP).
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.
Deutsches Institut für DemenzPrävention (DIDP), Neurodegeneration and Neurobiology, 66421 Homburg, Germany. marcus.grimm@uks.eu
Marcus O W
MO
Grimm
Tatjana L
TL
Rothhaar
Sven
S
Grösgen
Verena K
VK
Burg
Benjamin
B
Hundsdörfer
Viola J
VJ
Haupenthal
Petra
P
Friess
Stefan
S
Kins
Heike S
HS
Grimm
Tobias
T
Hartmann
D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D000072197:ADAM10 Protein; D000544:Alzheimer Disease / Q000235:genetics / Q000473:pathology; D053829:Amyloid Precursor Protein Secretases / Q000235:genetics / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D047468:Immunoprecipitation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009474:Neurons / Q000166:cytology; D058225:Plaque, Amyloid / Q000737:chemistry; D059748:Proteolysis; D044242:Trans Fatty Acids / Q000009:adverse effects*
D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D044242:Trans Fatty Acids; C413604:nicastrin protein; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human