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3 results on '"Anna K, Edlund"'

1. Brain integrity is altered by hepatic APOE ε4 in humanized-liver mice

Author

Andreas Giannisis, Kalicharan Patra, Anna K. Edlund, Lur Agirrezabala Nieto, Joan Benedicto-Gras, Simon Moussaud, Andrés de la Rosa, Daniel Twohig, Tore Bengtsson, Yuan Fu, Guojun Bu, Greg Bial, Lander Foquet, Christina Hammarstedt, Stephen Strom, Kristina Kannisto, Jacob Raber, Ewa Ellis, and Henrietta M. Nielsen

Subjects
Genotype, Apolipoprotein E4, Brain, Neurodegenerative Diseases, Mice, Cellular and Molecular Neuroscience, Psychiatry and Mental health, Apolipoproteins E, Liver, Mice, Inbred NOD, Alzheimer Disease, Animals, lipids (amino acids, peptides, and proteins), Molecular Biology, Biomarkers
Abstract

Liver-generated plasma apolipoprotein E (apoE) does not enter the brain but nonetheless correlates with Alzheimer’s disease (AD) risk and AD biomarker levels. Carriers of APOEε4, the strongest genetic AD risk factor, exhibit lower plasma apoE and altered brain integrity already at mid-life versus non-APOEε4 carriers. Whether altered plasma liver-derived apoE or specifically an APOEε4 liver phenotype promotes neurodegeneration is unknown. Here we investigated the brains of Fah−/−, Rag2−/−, Il2rg−/− mice on the Non-Obese Diabetic (NOD) background (FRGN) with humanized-livers of an AD risk-associated APOE ε4/ε4 versus an APOE ε2/ε3 genotype. Reduced endogenous mouse apoE levels in the brains of APOE ε4/ε4 liver mice were accompanied by various changes in markers of synaptic integrity, neuroinflammation and insulin signaling. Plasma apoE4 levels were associated with unfavorable changes in several of the assessed markers. These results propose a previously unexplored role of the liver in the APOEε4-associated risk of neurodegenerative disease.

Published
2022

2. Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis.

Author

Niina A Koistinen, Anna K Edlund, Preeti K Menon, Elena V Ivanova, Smaranda Bacanu, and Kerstin Iverfeldt

Subjects
Medicine, Science
Abstract

Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65. Furthermore, both ADAM10 and γ-secretase inhibitors decreased nuclear Fe65 in a similar way indicating an important role also of α-secretase in regulating nuclear translocation.

Published
2017
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3. Nuclear localization of amyloid-β precursor protein-binding protein Fe65 is dependent on regulated intramembrane proteolysis

Author

Niina A, Koistinen, Anna K, Edlund, Preeti K, Menon, Elena V, Ivanova, Smaranda, Bacanu, and Kerstin, Iverfeldt

Subjects
Cytoplasm, Subcellular Fractionation, Recombinant Fusion Proteins, Mutagenesis and Gene Deletion Techniques, Cell Membranes, Active Transport, Cell Nucleus, Electrophoretic Mobility Shift Assay, Nerve Tissue Proteins, Restriction Fragment Mapping, Research and Analysis Methods, Biochemistry, Cell Line, ADAM10 Protein, Amyloid beta-Protein Precursor, Protein Domains, Humans, Protein Interaction Domains and Motifs, Fractionation, Phosphorylation, Post-Translational Modification, Molecular Biology Techniques, Molecular Biology, Sequence Deletion, Neurons, Gene Mapping, Deletion Mutagenesis, Phosphatases, Membrane Proteins, Nuclear Proteins, Biology and Life Sciences, Proteins, Cell Biology, Enzymes, Separation Processes, Mutagenesis, Proteolysis, Enzymology, Amyloid Precursor Protein Secretases, Cellular Structures and Organelles, Protein Processing, Post-Translational, Research Article
Abstract

Fe65 is an adaptor protein involved in both processing and signaling of the Alzheimer-associated amyloid-β precursor protein, APP. Here, the subcellular localization was further investigated using TAP-tagged Fe65 constructs expressed in human neuroblastoma cells. Our results indicate that PTB2 rather than the WW domain is important for the nuclear localization of Fe65. Electrophoretic mobility shift of Fe65 caused by phosphorylation was not detected in the nuclear fraction, suggesting that phosphorylation could restrict nuclear localization of Fe65. Furthermore, both ADAM10 and γ-secretase inhibitors decreased nuclear Fe65 in a similar way indicating an important role also of α-secretase in regulating nuclear translocation.

Published
2016

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